Virus-specific CD4(+) memory-phenotype T cells are abundant in unexposed adults
Open accessAbstract
Although T cell memory is generally thought to require direct antigen exposure, we found an abundance of memory-phenotype cells (20%-90%, averaging over 50%) of CD4(+) T cells specific to viral antigens in adults who had never been infected. These cells express the appropriate memory markers and genes, rapidly produce cytokines, and have clonally expanded. In contrast, the same T cell receptor (TCR) specificities in newborns are almost entirely naïve, which might explain the vulnerability of young children to infections. One mechanism for this phenomenon is TCR cross-reactivity to environmental antigens, and in support of this, we found extensive cross-recognition by HIV-1 and influenza-reactive T lymphocytes to other microbial peptides and expansion of one of these after influenza vaccination. Thus, the presence of these memory-phenotype T cells has significant implications for immunity to novel pathogens, child and adult health, and the influence of pathogen-rich versus hygienic environments.
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Gut bacteria influence the development of Th17 cells, Treg cells and memory T cells.
“Gut bacteria influence the development of Th17 cells [46], Treg cells [47] and memory T cells [48–50].”
From Evolution of the immune system in humans from infancy to old age (2015) · cites this paper as [50]
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BackgroundSeveral Common HLA-DR Types Share Largely Overlapping Peptide Binding Repertoires
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BackgroundThe Crystal Structure of a T Cell Receptor in Complex with Peptide and MHC Class II
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Welsh, R. M., Che, J. W., Brehm, M. A., & Selin, L. K. (2010) · Immunological Reviews · doi:10.1111/j.0105-2896.2010.00897.x · Cited by 294 · cited 1× · see citing works
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“Second, we performed gene expression analysis for transcripts previously identified as being preferentially expressed in memory and naı̈ve human CD4 T cell populations (Haining et al., 2008; Weng et al., 2012).”
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“Consistent with these observations is the result of a randomized control trial involving over 6,000 children; it also showed a vaccine-dependent mortality reduction that was independent of measles-related death (Aaby et al., 2010).”
ResultCDR3 loop flexibility contributes to the degeneracy of TCR recognition
Reiser, J., Darnault, C., Grégoire, C., Mosser, T., Mazza, G., Kearney, A., van der Merwe, P. A., Fontecilla-Camps, J. C., Housset, D., & MALISSEN, B. (2003) · Nature Immunology · doi:10.1038/ni891 · Cited by 265 · cited 3× · see citing works
“Although it is also possible that our data reflect a potential bias of repertoires selected on the HLA-DR4 allele, this is still almost certainly an underestimate of the extent of cross-reactivity given that the propensity of T cells to cross-react with very different peptide sequences is well known and is probably di…”
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Prenatal or early postnatal events predict infectious deaths in young adulthood in rural Africa
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“The paucity of these cross-reactive cells could also help to explain why very young children are more susceptible to infectious diseases than are older ones (Casanova and Abel, 2005; Moore et al., 1999), and whether these responses are generated could mean the difference between survival and death.”
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“Although the prevalence of a naı̈ve phenotype in bulk cord blood T cells versus those in adults is well known (Cossarizza et al., 1996), the frequency and phenotype of individual TCR specificities are not.”
BackgroundGlobal epidemiology and control of Trichomonas vaginalis
Johnston, V. J., & Mabey, D. C. W. (2008) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0b013e3282f3d999 · Cited by 243 · cited 2× · see citing works
“We also detected donor-specific differences in that one donor’s cells responded to both F. magna and a second cross-reactive epitope from T. vaginalis, a common sexually transmitted infection (Johnston and Mabey, 2008).”
BackgroundHuman T-cell clones recognize chemically synthesized peptides of influenza haemagglutinin
Lamb, J. R., Eckels, D. D., Lake, P., Woody, J. N., & Green, N. H. (1982) · Nature · doi:10.1038/300066a0 · Cited by 223 · cited 1× · see citing works
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BackgroundGuimond, M., Veenstra, R. G., Grindler, D. J., Zhang, H., Cui, Y., Murphy, R. D., Kim, S. Y., Na, R., Hennighausen, L. G., Kurtuluş, S., et al. (2009) · Nature Immunology · doi:10.1038/ni.1695 · Cited by 218 · cited 2× · see citing works
“, 2004), but CD4 T cells appear to be less sensitive to homeostatic signals and differ from CD8 T cells in their TCR-dependent lipid-raft regulation and response to IL-7 signaling (Cho et al., 2010; Guimond et al., 2009).”
BackgroundInsulin as an autoantigen in NOD/human diabetes.
Zhang, L., Nakayama, M., & Eisenbarth, G. (2008) · Current Opinion in Immunology · doi:10.1016/j.coi.2007.11.005 · Cited by 215 · cited 2× · see citing works
“To broadly survey antigen-specific CD4+ T cells, we selected self-peptides from gp100, fibrinogen (Fib), or preproinsulin (PPins) for their relevance in antitumor responses and autoimmunity (Nielen et al., 2005; Yuan et al., 2009; Zhang et al., 2008).”
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“The dose and sequence of immunization appear to matter, and children given diphtheria-tetanuspertussis (DTP) vaccine after being immunized for measles have an increased risk of death and hospitalization, particularly if a high-titer measles vaccine is used (Aaby et al., 2003).”
BackgroundInborn errors of immunity to infection
Casanova, J., & Abel, L. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050854 · Cited by 187 · cited 1× · see citing works
“The paucity of these cross-reactive cells could also help to explain why very young children are more susceptible to infectious diseases than are older ones (Casanova and Abel, 2005; Moore et al., 1999), and whether these responses are generated could mean the difference between survival and death.”
BackgroundNielen, M. M. J., van der Horst, A. R., van Schaardenburg, D., van der Horst-Bruinsma, I. E., van de Stadt, R. J., Aarden, L. A., Dijkmans, B. A. C., & Hamann, D. (2005) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2004.029389 · Cited by 184 · cited 2× · see citing works
“To broadly survey antigen-specific CD4+ T cells, we selected self-peptides from gp100, fibrinogen (Fib), or preproinsulin (PPins) for their relevance in antitumor responses and autoimmunity (Nielen et al., 2005; Yuan et al., 2009; Zhang et al., 2008).”
BackgroundT Cell Receptor-Dependent Regulation of Lipid Rafts Controls Naive CD8+ T Cell Homeostasis
Cho, J.-H., Kim, H.-O., Surh, C. D., & Sprent, J. (2010) · Immunity · doi:10.1016/j.immuni.2009.11.014 · Cited by 154 · cited 2× · see citing works
“, 2004), but CD4 T cells appear to be less sensitive to homeostatic signals and differ from CD8 T cells in their TCR-dependent lipid-raft regulation and response to IL-7 signaling (Cho et al., 2010; Guimond et al., 2009).”
BackgroundDerivation and Maintenance of Virtual Memory CD8 T Cells
Akue, A. D., Lee, J., & Jameson, S. C. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1102213 · Cited by 150 · cited 3× · see citing works
“Antigen-specific precursor memory cells have subsequently been found in other mouse studies and have been shown to be generated in the periphery during neonatal lymphopenia and to thereafter be stably maintained and increase with age (Akue et al., 2012; Decman et al., 2012; Rudd et al., 2011).”
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“Antigen-specific precursor memory cells have subsequently been found in other mouse studies and have been shown to be generated in the periphery during neonatal lymphopenia and to thereafter be stably maintained and increase with age (Akue et al., 2012; Decman et al., 2012; Rudd et al., 2011).”
BackgroundSette, A., Sidney, J., Oseroff, C., del Guercio, M. F., Southwood, S., Arrhenius, T. S., Powell, M. F., Colon, S. M., Gaeta, F. C., & Grey, H. M. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.6.3163 · Cited by 148 · cited 14× · see citing works
“…of three independent experiments (see also Figure S5). registers: HIV-1 167–179 was previously shown to bind a similar DR allele (Zavala-Ruiz et al., 2004), and HIV-1 171–181 contains the predicted anchor residues for HLA-DR4 (Hammer et al., 1994; Sette et al., 1993; Southwood et al., 1998).”
BackgroundInfluentialMin, B., Foucras, G., Meier‐Schellersheim, M., & Paul, W. E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400606101 · Cited by 148 · cited 2× · see citing works
“For CD4+ T cells, homeostatic proliferation also induces memory-phenotype T cells in lymphopenic animals (Min et al., 2004), but CD4+ T cells appear to be less sensitive to homeostatic signals and differ from CD8+ T cells in their TCR-dependent lipid-raft regulation and response to IL-7 signaling…”
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“…basis of T cell stimulation and evidence that they are the product of natural processing and presentation (Alexander et al., 2010; Arif et al., 2004; Auger et al., 2005; Bronke et al., 2005; Diethelm-Okita et al., 1997; Lamb et al., 1982; Norris et al., 2004; Novak et al., 2001; Phan et al., 2003).”
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“Antigen-specific precursor memory cells have subsequently been found in other mouse studies and have been shown to be generated in the periphery during neonatal lymphopenia and to thereafter be stably maintained and increase with age (Akue et al., 2012; Decman et al., 2012; Rudd et al., 2011).”
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“…of three independent experiments (see also Figure S5). registers: HIV-1 167–179 was previously shown to bind a similar DR allele (Zavala-Ruiz et al., 2004), and HIV-1 171–181 contains the predicted anchor residues for HLA-DR4 (Hammer et al., 1994; Sette et al., 1993; Southwood et al., 1998).”
BackgroundKwok, W. W., Tan, V., Gillette, L., Littell, C. T., Soltis, M. A., LaFond, R. E., Yang, J., James, E. A., & DeLong, J. H. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1102190 · Cited by 120 · cited 2× · see citing works
“Very recent work measuring the frequency of precursor cells recognizing Bacillus anthracis found a similar frequency range (Kwok et al., 2012).”
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“…basis of T cell stimulation and evidence that they are the product of natural processing and presentation (Alexander et al., 2010; Arif et al., 2004; Auger et al., 2005; Bronke et al., 2005; Diethelm-Okita et al., 1997; Lamb et al., 1982; Norris et al., 2004; Novak et al., 2001; Phan et al., 2003).”
BackgroundExpression and kinetics of cytokines determined by intracellular staining using flow cytometry
Winkler, B., Schlenke, P., & Seyfarth, M. (1999) · Journal of Immunological Methods · doi:10.1016/s0022-1759(98)00200-2 · Cited by 106 · cited 1× · see citing works
“First, we examined their cytokine responses because memory cells are known to produce cytokines more rapidly and in larger amounts than naı̈ve T cells (Mascher et al., 1999).”
BackgroundAuger, I., Sebbag, M., Vincent, C., Balandraud, N., Guis, S., Nogueira, L., Svensson, B., Cantagrel, A. G., Serre, G., & Roudier, J. (2005) · Arthritis & Rheumatism · doi:10.1002/art.21391 · Cited by 106 · cited 2× · see citing works
“…basis of T cell stimulation and evidence that they are the product of natural processing and presentation (Alexander et al., 2010; Arif et al., 2004; Auger et al., 2005; Bronke et al., 2005; Diethelm-Okita et al., 1997; Lamb et al., 1982; Norris et al., 2004; Novak et al., 2001; Phan et al., 2003).”
BackgroundVeirum, J. E., Sodemann, M., Biai, S., Jakobsen, M., Garly, M., Hedegaard, K. L., Jensen, H., & Aaby, P. (2004) · Vaccine · doi:10.1016/j.vaccine.2004.02.053 · Cited by 84 · cited 1× · see citing works
“For example, several large retrospective and longitudinal studies on young children have found a survival benefit from measles vaccines even when death from measles was excluded (Kristensen et al., 2000; Veirum et al., 2005).”
BackgroundYuan, J. D., Ku, G. Y., Gallardo, H. F., Orlandi, F., Manukian, G., Rasalan, T. S., Xu, Y., Li, H., Vyas, S., Mu, Z., et al. (2009) · PubMed Central · Cited by 80 · see citing works
Zavala‐Ruiz, Z., Strug, I., Walker, B. D., Norris, P. J., & Stern, L. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403371101 · Cited by 67 · cited 2× · see citing works
“…are representative of three independent experiments (see also Figure S5). registers: HIV-1 167–179 was previously shown to bind a similar DR allele (Zavala-Ruiz et al., 2004), and HIV-1 171–181 contains the predicted anchor residues for HLA-DR4 (Hammer et al., 1994; Sette et al., 1993; Southwood…”
BackgroundNewell, E. W., Ely, L. K., Kruse, A. C., Reay, P. A., Rodriguez, S. N., Lin, A. E., Kuhns, M. S., García, K. C., & Davis, M. M. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100197 · Cited by 66 · cited 3× · see citing works
“Although it is also possible that our data reflect a potential bias of repertoires selected on the HLA-DR4 allele, this is still almost certainly an underestimate of the extent of cross-reactivity given that the propensity of T cells to cross-react with very different peptide sequences is well known and is probably di…”
BackgroundSelf-citationLevy, P., Fenollar, F., Stein, A., Borrione, F., & Raoult, D. (2009) · Clinical Infectious Diseases · doi:10.1086/605672 · Cited by 59 · cited 2× · see citing works
“magna, a human commensal bacteria (Levy et al., 2009), are both stimulated to proliferate and have the typical rise and fall of tetramer-positive T cells after vaccination.”
BackgroundAlexander, J., Bilsel, P., del Guercio, M., Stewart, S., Marinkovic-Petrovic, A., Southwood, S., Crimi, C., Vang, L., Walker, L., Ishioka, G. Y., et al. (2009) · Vaccine · doi:10.1016/j.vaccine.2009.10.103 · Cited by 51 · cited 2× · see citing works
“…were chosen from the literature on the basis of T cell stimulation and evidence that they are the product of natural processing and presentation (Alexander et al., 2010; Arif et al., 2004; Auger et al., 2005; Bronke et al., 2005; Diethelm-Okita et al., 1997; Lamb et al., 1982; Norris et al.,…”
MethodChu, H., Moon, J. J., Kruse, A. C., Pepper, M., & Jenkins, M. K. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1002276 · Cited by 43 · cited 2× · see citing works
“Studies on precursor CD4 T cells in immunocompetent mice have generally found these cells to have a naı̈ve phenotype (Chu et al., 2010; Moon et al., 2007).”
BackgroundDiethelm-Okita, B. M., Raju, R. P., Okita, D. K., & Conti‐Fine, B. M. (1997) · The Journal of Infectious Diseases · doi:10.1093/infdis/175.2.382 · Cited by 39 · cited 2× · see citing works
“…basis of T cell stimulation and evidence that they are the product of natural processing and presentation (Alexander et al., 2010; Arif et al., 2004; Auger et al., 2005; Bronke et al., 2005; Diethelm-Okita et al., 1997; Lamb et al., 1982; Norris et al., 2004; Novak et al., 2001; Phan et al., 2003).”
BackgroundFine Specificity and Cross-Clade Reactivity of HIV Type 1 Gag-Specific CD4 + T Cells
Norris, P. J., Moffett, H. F., Brander, C., Allen, T. M., O'Sullivan, K. M., Cosimi, L. A., Kaufmann, D., Walker, B. D., & Rosenberg, E. S. (2004) · AIDS Research and Human Retroviruses · doi:10.1089/088922204322996554 · Cited by 36 · cited 2× · see citing works
“…basis of T cell stimulation and evidence that they are the product of natural processing and presentation (Alexander et al., 2010; Arif et al., 2004; Auger et al., 2005; Bronke et al., 2005; Diethelm-Okita et al., 1997; Lamb et al., 1982; Norris et al., 2004; Novak et al., 2001; Phan et al., 2003).”
BackgroundRandomized Trials to Study the Nonspecific Effects of Vaccines in Children in Low-Income Countries
Shann, F. A., Nohynek, H., Scott, J. A. G., Hesseling, A. C., & Flanagan, K. L. (2010) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0b013e3181c91361 · Cited by 33 · cited 1× · see citing works
“In humans, there is also a growing recognition that vaccinations and their sequence of exposure can have a more general impact on morbidity and mortality beyond the expected benefit in preventing the targeted disease (Shann et al., 2010).”
BackgroundHigh-throughput gene expression profiling of memory differentiation in primary human T cells
Haining, W. N., Angelosanto, J., Brosnahan, K., Ross, K. N., Hahn, C. K., Russell, K. E. R., Drury, L., Norton, S., Nadler, L. M., & Stegmaier, K. (2008) · BMC Immunology · doi:10.1186/1471-2172-9-44 · Cited by 30 · cited 2× · see citing works
“Second, we performed gene expression analysis for transcripts previously identified as being preferentially expressed in memory and naı̈ve human CD4 T cell populations (Haining et al., 2008; Weng et al., 2012).”
MethodBronke, C., Palmer, N. M., Westerlaken, G. H. A., Toebes, M., van Schijndel, G. M. W., Purwaha, V., van Meijgaarden, K. E., Schumacher, T. N., van Baarle, D., Tesselaar, K., et al. (2005) · Human Immunology · doi:10.1016/j.humimm.2005.06.011 · Cited by 16 · cited 2× · see citing works
“…basis of T cell stimulation and evidence that they are the product of natural processing and presentation (Alexander et al., 2010; Arif et al., 2004; Auger et al., 2005; Bronke et al., 2005; Diethelm-Okita et al., 1997; Lamb et al., 1982; Norris et al., 2004; Novak et al., 2001; Phan et al., 2003).”
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Role of the microbiota in immunity and inflammation.
Belkaid, Y., & Hand, T. W. (2014) · Cell · doi:10.1016/j.cell.2014.03.011 · Cited by 5,385 · see citing works
“In addition, recent studies suggest that CD4 T cell clones that are cross-reactive to commensals and viruses are common in healthy individuals (Su et al., 2013).”
BackgroundInfluentialSARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls
Le Bert, N., Tan, A. T., Kunasegaran, K., Tham, C. Y. L., Hafezi, M., Chia, A., Chng, M. H. Y., Lin, M., Tan, N., Linster, M., et al. (2020) · Nature · doi:10.1038/s41586-020-2550-z · Cited by 1,887 · see citing works
Regulatory T cells in cancer immunotherapy
Tanaka, A., & Sakaguchi, S. (2017) · Cell Research · doi:10.1038/cr.2016.151 · Cited by 1,860 · see citing works
Evolution of the immune system in humans from infancy to old age
Simon, A. K., Hollander, G. A., & McMichael, A. (2015) · Proceedings of the Royal Society B: Biological Sciences · doi:10.1098/rspb.2014.3085 · Cited by 1,796 · see citing works
CTLA-4: a moving target in immunotherapy
Rowshanravan, B., Halliday, N., & Sansom, D. M. (2018) · Blood · doi:10.1182/blood-2017-06-741033 · Cited by 1,233 · see citing works
Variation in the Human Immune System Is Largely Driven by Non-Heritable Influences
Brodin, P., Jojic, V., Gao, T., Bhattacharya, S., Angel, C. J. L., Furman, D., Shen-Orr, S., Dekker, C. L., Swan, G. E., Butte, A. J., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.020 · Cited by 1,065 · see citing works
“Adaptations of the immune system with time could be the result of well-known immune mechanisms, such as specific antibodies and T cells or cross-reactive immunity (Su et al., 2013), or some as yet to be defined maturational process.”
BackgroundSelf-citationGuidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
Cossarizza, A., Chang, H., Radbruch, A., Acs, A., Adam, D., Adam‐Klages, S., Agace, W. W., Aghaeepour, N., Akdiş, M., Allez, M., et al. (2019) · European Journal of Immunology · doi:10.1002/eji.201970107 · Cited by 982 · see citing works
Human memory T cells: generation, compartmentalization and homeostasis
Farber, D. L., Yudanin, N. A., & Restifo, N. P. (2014) · Nature Reviews Immunology · doi:10.1038/nri3567 · Cited by 897 · see citing works
Understanding immunosenescence to improve responses to vaccines
Goronzy, J. J., & Weyand, C. M. (2013) · Nature Immunology · doi:10.1038/ni.2588 · Cited by 827 · see citing works
Diversity and clonal selection in the human T-cell repertoire
Qi, Q., Liu, Y., Cheng, Y., Glanville, J., Zhang, D., Lee, J.-Y., Olshen, R. A., Weyand, C. M., Boyd, S. D., & Goronzy, J. J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1409155111 · Cited by 755 · see citing works
“Tetramer studies in noninfected individuals have suggested that the frequency of T cells specific for many exogenous viral peptides, or self-peptides, is on the order of 1 in 1 million (29), suggesting that the estimated elderly repertoires of more than 100 million TCR α-β dimers could be diverse enough to recognize m…”
BackgroundRook, G. A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1313731110 · Cited by 760 · see citing works
Furman, D., Hejblum, B. P., Simon, N., Jojic, V., Dekker, C. L., Thiébaut, R., Tibshirani, R. J., & Davis, M. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321060111 · Cited by 678 · see citing works
Self-citationImmune determinants of COVID-19 disease presentation and severity
Brodin, P. (2021) · Nature Medicine · doi:10.1038/s41591-020-01202-8 · Cited by 654 · see citing works
SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition
Nelde, A., Bilich, T., Heitmann, J. S., Maringer, Y., Salih, H. R., Roerden, M., Lübke, M., Bauer, J., Rieth, J., Wacker, M., et al. (2021) · Nature Immunology · doi:10.1038/s41590-020-00808-x · Cited by 582 · see citing works
Guidelines for the use of flow cytometry and cell sorting in immunological studies *
Cossarizza, A., Chang, H., Radbruch, A., Akdiş, M., Andrä, I., Annunziato, F., Bächer, P., Barnaba, V., Battistini, L., Bauer, W. M., et al. (2017) · European Journal of Immunology · doi:10.1002/eji.201646632 · Cited by 572 · see citing works
Understanding subset diversity in T cell memory
Jameson, S. C., & Masopust, D. (2018) · Immunity · doi:10.1016/j.immuni.2018.02.010 · Cited by 523 · see citing works
“Antigen cross-reactivity is hard to rule out as a potential mechanism for memory CD4+ T cell maintenance, especially in humans where uncharacterized sequential infections may occur regularly – indeed, Davis’ group recently proposed that many human CD4+ T cells specific for novel foreign antigens are already of memory-…”
Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
Cossarizza, A., Chang, H., Radbruch, A., Abrignani, S., Addo, R., Akdis, M., Andrä, I., Andreata, F., Annunziato, F., Arranz, E., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202170126 · Cited by 531 · see citing works
A small jab – a big effect: nonspecific immunomodulation by vaccines
Benn, C. S., Netea, M. G., Selin, L. K., & Aaby, P. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.04.004 · Cited by 517 · see citing works
Microbiome and Anticancer Immunosurveillance
Zitvogel, L., Ayyoub, M., Routy, B., & Kroemer, G. (2016) · Cell · doi:10.1016/j.cell.2016.03.001 · Cited by 478 · see citing works
T cell receptor signalling networks: branched, diversified and bounded
Brownlie, R. J., & Zamoyska, R. (2013) · Nature Reviews Immunology · doi:10.1038/nri3403 · Cited by 453 · see citing works
Human Anti-fungal Th17 Immunity and Pathology Rely on Cross-Reactivity against Candida albicans
Bacher, P., Hohnstein, T., Beerbaum, E., Röcker, M., Blango, M. G., Kaufmann, S., Röhmel, J., Eschenhagen, P., Grehn, C., Seidel, K., et al. (2019) · Cell · doi:10.1016/j.cell.2019.01.041 · Cited by 473 · see citing works
Scally, S. W., Petersen, J., Law, S. C., Dudek, N. L., Nel, H. J., Loh, K. L., Wijeyewickrema, L. C., Eckle, S. B. G., van Heemst, J., Pike, R. N., et al. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20131241 · Cited by 429 · see citing works
“This is consistent with recent findings in healthy HLA-DRB1*0401+ individuals, where self-antigen–specific CD4+ T cells were observed in preenriched samples, despite the donors not suffering from autoimmune disease (Su et al., 2013).”
ResultFlandroy, L., Poutahidis, T., Berg, G., Clarke, G. A., Dao, M. C., Decaestecker, E., Furman, E., Haahtela, T., Massart, S., Plovier, H., et al. (2018) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2018.01.288 · Cited by 399 · see citing works
“These cells have the typical properties of memory T cells, and were shown to cross-react with other organisms from the environment (Su et al., 2013).”
The impact of the gut microbiome on extra-intestinal autoimmune diseases
Miyauchi, E., Shimokawa, C., Steimle, A., Desai, M. S., & Ohno, H. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00727-y · Cited by 375 · see citing works
Bacher, P., Rosati, E., Esser, D., Martini, G. R., Saggau, C., Schiminsky, E., Dargvainiene, J., Schröder, I., Wieters, I., Khodamoradi, Y., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.11.016 · Cited by 314 · see citing works
“…pre-existing immunity also exists against several other pathogens and neoantigens (Bacher et al., 2013; Campion et al., 2014; Kwok et al., 2012; Su et al., 2013) and is associated with variable clinical consequences, ranging from protective to harmful immune responses (Bacher et al., 2019;…”
InfluentialNaive T Cell Maintenance and Function in Human Aging
Goronzy, J. J., Fang, F., Cavanagh, M., Qi, Q., & Weyand, C. M. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500046 · Cited by 348 · see citing works
“(84) described that healthy individuals carry memory T cells to Ags they have never encountered in life.”
BackgroundHegazy, A. N., West, N. R., Stubbington, M. J. T., Wendt, E., Suijker, K. I. M., Datsi, A., This, S., Danne, C., Campion, S., Duncan, S. H., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.07.047 · Cited by 338 · see citing works
Cytomegalovirus infection enhances the immune response to influenza
Furman, D., Jojic, V., Sharma, S., Shen-Orr, S. S., L. Angel, C. J., Onengut-Gumuscu, S., Kidd, B. A., Maecker, H. T., Concannon, P., Dekker, C. L., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa2293 · Cited by 332 · see citing works
“(66) have proposed that T cell cross-reactivity could be a factor based on the observation that healthy adults can have large numbers of memory phenotype CD4 T cells specific for viral epitopes to which those individuals had never been exposed.”
Self-citationCommensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus
Greiling, T. M., Dehner, C. A., Chen, X., Hughes, K., Iñiguez, A. J., Boccitto, M., Zegarra-Ruiz, D. F., Renfroe, S. C., Vieira, S. M., Ruff, W. E., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aan2306 · Cited by 324 · see citing works
“Studies of the normal human gut have shown that the generation of commensalreactive antibodies and T cell receptors (TCRs) is both abundant and physiologic (16, 17).”
BackgroundRole of Different Subpopulations of CD8+ T Cells during HIV Exposure and Infection
González, S. M., Taborda, N. A., & Rugeles, M. T. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00936 · Cited by 323 · see citing works
“Nonetheless, it could also be related to the presence of a heterologous T cell response to similar antigens (32).”
BackgroundSibener, L. V., Fernandes, R. A., Kolawole, E. M., Carbone, C. B., Liu, F., McAffee, D. B., Birnbaum, M. E., Yang, X., Su, L. F., Yu, W., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.017 · Cited by 312 · see citing works
“…biology approaches to understand vaccine responses (Furman et al., 2013), twin studies to understand the relative influence of environment versus genetics (ongoing) and T cell repertoire studies to understand self vs non-self capabilities and the origin of memory T cell responses (Su et al 2013).”
Self-citationGut Microbiota Regulation of T Cells During Inflammation and Autoimmunity
Brown, E., Kenny, D. J., & Xavier, R. J. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041841 · Cited by 310 · see citing works
Clonal Deletion Prunes but Does Not Eliminate Self-Specific αβ CD8+ T Lymphocytes
Yu, W., Jiang, N. J., Ebert, P. J. R., Kidd, B. A., Müller, S., Lund, P. J., Juang, J., Adachi, K., Tse, T., Birnbaum, M. E., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.05.001 · Cited by 301 · see citing works
“This agrees roughly with the naive T cell frequencies measured in mice (1:104–1:106) and correlates well with the values reported recently in humans (Moon et al., 2007; Kotturi et al., 2008; Obar et al., 2008; Alanio et al., 2010; Schmidt et al., 2011; Su et al., 2013).”
InfluentialSelf-citationLynn, D. J., Benson, S. C., Lynn, M. A., & Pulendran, B. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00554-7 · Cited by 300 · see citing works
Influence of immune aging on vaccine responses
Gustafson, C. E., Kim, C., Weyand, C. M., & Goronzy, J. J. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.03.017 · Cited by 286 · see citing works
Aging of the T Cell Compartment in Mice and Humans: From No Naive Expectations to Foggy Memories
Nikolich-Žugich, J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401174 · Cited by 259 · see citing works
“However, at a minimum, this result strongly suggests that although CD8 T cells with increased TCR avidity (33) and/or CD4 T cells with increased cross-reactivity (41) (M.”
ResultBloomfield, S. F., Rook, G. A. W., Scott, E. A., Shanahan, F., Stanwell-Smith, R., & Turner, P. (2016) · Perspectives in Public Health · doi:10.1177/1757913916650225 · Cited by 274 · see citing works
“45 What are the likely causes of reduced or altered microbial exposures in order to look for strategies which might restore the necessary microbial exposures, it is first necessary to understand the underlying causes of the loss of exposure.”
BackgroundLi, J., Zaslavsky, M., Su, Y., Guo, J., Sikora, M. J., van Unen, V., Christophersen, A., Chiou, S.-H., Chen, L., Li, J., et al. (2022) · Science · doi:10.1126/science.abi9591 · Cited by 249 · see citing works
“Although it was previously accepted that most self-specific T cells were eliminated in the thymus, recent work has shown that many such cells survive and populate the periphery of both humans and mice (18, 19).”
BackgroundSelf-citationHarnessing the beneficial heterologous effects of vaccination
Goodridge, H. S., Ahmed, S., Curtis, N. C., Kollmann, T. R., Levy, O., Netea, M. G., Pollard, A. J., van Crevel, R., & Wilson, C. B. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.43 · Cited by 257 · see citing works
Evolution, human-microbe interactions, and life history plasticity
Rook, G., Bäckhed, F., Levin, B. R., McFall-Ngai, M. J., & McLean, A. R. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30566-4 · Cited by 246 · see citing works
“6 development, 39) expansion, level of background activation,((40)) and memory repertoire,((41)) of the lymphoid system.”
BackgroundAn Introduction to Complex Systems Science and Its Applications
Siegenfeld, A. F., & Bar-Yam, Y. (2020) · Complexity · doi:10.1155/2020/6105872 · Cited by 305 · see citing works
“Immune system performance is improved by early exposure to non-lethal pathogens [37, 38]; muscles and bones are strengthened by micro-tears and micro-fractures, respectively; we learn by exposure to new information and problem-solving; and our psychologies are strengthened by exposure to adversity, provided the advers…”
BackgroundLegoux, F. P., Lim, J., Cauley, A. W., Dikiy, S., Ertelt, J. M., Mariani, T. J., Sparwasser, T. D., Way, S. S., & Moon, J. J. (2015) · Immunity · doi:10.1016/j.immuni.2015.10.011 · Cited by 238 · see citing works
“Our findings are congruous with recent tetramer-based studies by Davis and colleagues showing that the frequencies of several self antigen-specific T cell populations in humans are in the same range as frequencies for foreign antigen-specific populations (Su et al., 2013; Yu et al., 2015).”
An Introduction to Complex Systems Science and Its Applications
Siegenfeld, A. F., & Yaneer Bar-yam, A. (2020) · RePEc: Research Papers in Economics · Cited by 236 · see citing works
Automatic Classification of Cellular Expression by Nonlinear Stochastic Embedding (ACCENSE)
Shekhar, K., Brodin, P., Davis, M. M., & Chakraborty, A. K. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321405111 · Cited by 215 · see citing works
“Traditionally, it was believed that naive cells differentiate to acquire a memory phenotype only upon antigen encounter, but this may also occur in the context of homeostatic proliferation (16), or T-cell receptor (TCR) cross-reactivity (17).”
BackgroundSelf-citationSomatic Mutations and Neoepitope Homology in Melanomas Treated with CTLA-4 Blockade
Nathanson, T., Ahuja, A., Rubinsteyn, A., Aksoy, B. A., Hellmann, M. D., Miao, D., Allen, E. M. V., Merghoub, T., Wolchok, J. D., Snyder, A., et al. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0019 · Cited by 208 · see citing works
Microbial ‘old friends’, immunoregulation and socioeconomic status
Rook, G. A. W., Raison, C. L., & Lowry, C. A. (2014) · Clinical & Experimental Immunology · doi:10.1111/cei.12269 · Cited by 207 · see citing works
A conserved human T cell population targets mycobacterial antigens presented by CD1b
Rhijn, I. V., Kasmar, A. G., de Jong, A., Gras, S., Bhati, M., Doorenspleet, M. E., de Vries, N., Godfrey, D. I., Altman, J. D., de Jager, W., et al. (2013) · Nature Immunology · doi:10.1038/ni.2630 · Cited by 201 · see citing works
Han, A. S., Newell, E. W., Glanville, J., Fernandez‐Becker, N., Khosla, C., Chien, Y., & Davis, M. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1311861110 · Cited by 194 · see citing works
Self-citationHow many TCR clonotypes does a body maintain?
Lythe, G., Callard, R. E., Hoare, R. L., & Molina-París, C. (2016) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2015.10.016 · Cited by 175 · see citing works
“We take the value of p, the probability that interaction with a given self pMHC is capable of causing a randomly-selected T cell to divide, to be the same in humans and mice: p¼ 10 6 (Rizzuto et al., 2009; Su et al., 2013; Jenkins et al., 2009).”
BackgroundDiet, microbiota and autoimmune diseases
Vieira, S., Pagovich, O., & Kriegel, M. A. (2014) · Lupus · doi:10.1177/0961203313501401 · Cited by 193 · see citing works
Estimating the Diversity, Completeness, and Cross-Reactivity of the T Cell Repertoire
Zarnitsyna, V. I., Evavold, B. D., Schoettle, L. N., Blattman, J. N., & Antia, R. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00485 · Cited by 180 · see citing works
Kimura, T., Kobiyama, K., Winkels, H., Tse, K. Y., Miller, J. F., Vassallo, M., Wolf, D., Ryden, C., Orecchioni, M., Dileepan, T., et al. (2018) · Circulation · doi:10.1161/circulationaha.117.031420 · Cited by 178 · see citing works
Christophersen, A., Lund, E. G., Snir, O., Solà, E., Kanduri, C., Dahal-Koirala, S., Zühlke, S., Molberg, Ø., Utz, P. J., Rohani-Pichavant, M., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0403-9 · Cited by 164 · see citing works
Self-citationMills, J. G., Weinstein, P., Gellie, N. J. C., Weyrich, L. S., Lowe, A. J., & Breed, M. F. (2017) · Restoration Ecology · doi:10.1111/rec.12610 · Cited by 172 · see citing works
“For example, microorganisms help guide immunoregulation by inducing regulatory T cells which attenuate allergic airway responses, and by stimulating memory-phenotype T cells for viral antigens that the host has not been exposed to (Karimi et al. 2009; Su et al. 2013).”
BackgroundAntigen-inexperienced memory CD8+ T cells: where they come from and why we need them
White, J. T., Cross, E. W., & Kedl, R. M. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.34 · Cited by 170 · see citing works
T follicular helper cells and T follicular regulatory cells in rheumatic diseases
Deng, J., Wei, Y., Fonseca, V. R., Graça, L., & Yu, D. (2019) · Nature Reviews Rheumatology · doi:10.1038/s41584-019-0254-2 · Cited by 169 · see citing works
Herati, R. S., Muselman, A., Vella, L., Bengsch, B., Parkhouse, K., Del Alcazar, D., Kotzin, J., Doyle, S. A., Tebas, P., Hensley, S. E., et al. (2017) · Science Immunology · doi:10.1126/sciimmunol.aag2152 · Cited by 167 · see citing works
“To test this idea, we sorted HA308–316or HA398–410-positive CD4 T cells at 6 months after vaccination.”
BackgroundMethodInfluentialFunctionally diverse human T cells recognize non-microbial antigens presented by MR1
Lepore, M., Kalinichenko, A., Calogero, S., Kumar, P., Paleja, B. S., Schmaler, M., Narang, V., Zolezzi, F., Poidinger, M., Mori, L., et al. (2017) · eLife · doi:10.7554/elife.24476 · Cited by 164 · see citing works
“This estimated frequency, although representing an approximation, is within the range of the frequency of peptidespecific CD4+ T cells after antigen exposure (Lucas et al., 2004; Su et al., 2013).”
BackgroundResultWolf, D., Gerhardt, T., Winkels, H., Michel, N. A., Pramod, A. B., Ghosheh, Y., Brunel, S., Buscher, K., Miller, J., McArdle, S., et al. (2020) · Circulation · doi:10.1161/circulationaha.119.042863 · Cited by 164 · see citing works
Mallajosyula, V. V. A., Ganjavi, C., Chakraborty, S., McSween, A. M., Pavlovitch-Bedzyk, A. J., Wilhelmy, J., Nau, A. N., Manohar, M., Nadeau, K. C., & Davis, M. M. (2021) · Science Immunology · doi:10.1126/sciimmunol.abg5669 · Cited by 161 · see citing works
“TCR cross-reactivity or environmental exposures (39).”
Self-citationNelson, R. W., Beisang, D. J., Tubo, N. J., Dileepan, T., Wiesner, D. L., Nielsen, K., Wüthrich, M., Klein, B. S., Kotov, D. I., Spanier, J. A., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.12.022 · Cited by 163 · see citing works
“Recent progress, however, has been made in this area for p:MHCII-specific TCRs expressed by CD4+ T cells (Birnbaum et al., 2014; Lucca et al., 2014; Su et al., 2013).”
InfluentialFlow-cytometric analysis of rare antigen-specific T cells
Bacher, P., & Scheffold, A. (2013) · Cytometry Part A · doi:10.1002/cyto.a.22317 · Cited by 155 · see citing works
“However, we could furthermore demonstrate that about on third of the identified neo- or auto-antigenspecific CD154(1) T cells in healthy donors had a memory phenotype, suggesting that these cells are the result of priming by cross-reactivity, which extends the findings by Mark Davis group for virus-specific T cells us…”
BackgroundResultMurray, A. J., Kwon, K. J., Färber, D. L., & Siliciano, R. F. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600343 · Cited by 154 · see citing works
“However, human memory CD4 T cells exhibit cross-reactivity, and specificities for Ags never encountered can be detected among memory CD4 T cells in peripheral blood (176).”
BackgroundT cells in the control of organ-specific autoimmunity
Bluestone, J. A., Bour-Jordan, H., Cheng, M., & Anderson, M. (2015) · Journal of Clinical Investigation · doi:10.1172/jci78089 · Cited by 155 · see citing works
Ruff, W. E., Dehner, C. A., Kim, W. J., Pagovich, O. E., Aguiar, C. L., Yu, A., Roth, A. S., Vieira, S. M., Kriegel, C., Adeniyi, O., et al. (2019) · Cell Host & Microbe · doi:10.1016/j.chom.2019.05.003 · Cited by 155 · see citing works
HIV-Host Interactions: Implications for Vaccine Design
Haynes, B. F., Shaw, G. M., Korber, B., Kelsoe, G. H., Sodroski, J., Hahn, B. H., Borrow, P., & McMichael, A. J. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.02.002 · Cited by 150 · see citing works
“The pre-existing CD4 T cell repertoire in HIV-1 uninfected individuals also contains T cells that cross-react with both HIV-1 and microbiome peptides (Campion et al., 2014; Su et al., 2013).”
BackgroundRoberto, A., Castagna, L., Zanon, V., Bramanti, S., Crocchiolo, R., McLaren, J. E., Gandolfi, S., Tentorio, P., Sarina, B., Timofeeva, I., et al. (2015) · Blood · doi:10.1182/blood-2014-11-608406 · Cited by 149 · see citing works
Sizing up the key determinants of the CD8+ T cell response
Tscharke, D. C., Croft, N. P., Doherty, P. C., & Gruta, N. L. L. (2015) · Nature reviews. Immunology · doi:10.1038/nri3905 · Cited by 148 · see citing works
Shaping Variation in the Human Immune System
Liston, A., Carr, E. J., & Linterman, M. A. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.08.002 · Cited by 145 · see citing works
Immune deficiency and autoimmunity in patients with CTLA-4 (CD152) mutations
Verma, N., Burns, S. O., Walker, L. S. K., & Sansom, D. M. (2017) · Clinical & Experimental Immunology · doi:10.1111/cei.12997 · Cited by 136 · see citing works
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Self-citationBeyond model antigens: high-dimensional methods for the analysis of antigen-specific T cells
Newell, E. W., & Davis, M. M. (2014) · Nature Biotechnology · doi:10.1038/nbt.2783 · Cited by 129 · see citing works
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New approaches to understanding the immune response to vaccination and infection
Furman, D., & Davis, M. M. (2015) · Vaccine · doi:10.1016/j.vaccine.2015.06.117 · Cited by 130 · see citing works
Self-citationHigh-affinity oligoclonal TCRs define effective adoptive T cell therapy targeting mutant KRAS-G12D
Sim, M. J. W., Lu, J., Spencer, M. K., Hopkins, F. R., Tran, E., Rosenberg, S. A., Long, E. O., & Sun, P. D. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1921964117 · Cited by 123 · see citing works
Jameson, S. C., Lee, Y. J., & Hogquist, K. A. (2015) · Advances in immunology · doi:10.1016/bs.ai.2014.12.001 · Cited by 125 · see citing works
Heterologous Immunity: Role in Natural and Vaccine-Induced Resistance to Infections
Agrawal, B. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02631 · Cited by 123 · see citing works
Standing on the shoulders of mice
Medetgul-Ernar, K., & Davis, M. M. (2022) · Immunity · doi:10.1016/j.immuni.2022.07.008 · Cited by 119 · see citing works
Self-citationAutoimmune host–microbiota interactions at barrier sites and beyond
Ruff, W. E., & Kriegel, M. A. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.02.006 · Cited by 122 · see citing works
“While crossreactivity to commensals has not been proven to drive autoimmunity, recent work has established that commensals can induce crossreactive lymphocytes, which may have evolved to increase host fitness [106].”
BackgroundInfluentialMicrobiota, immunoregulatory old friends and psychiatric disorders
Rook, G. A. W., Raison, C. L., & Lowry, C. A. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-0897-4_15 · Cited by 117 · see citing works
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“The presence of CD4+ memory T cells cross-reactive with both HIV-1 antigens and microbial peptides in uninfected adults (Campion et al., 2014; Su et al., 2013), and the 5.2% and 11.9% VH mutation frequencies of DH306 and DH309, suggested that the affinity maturation of gp41 commensal bacteria…”
BackgroundInfluentialMolecular mechanisms of CD8+ T cell trafficking and localization
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“reactivity (36), exhibited the VM phenotype, and we call them here aging-related VM cells .”
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Genetic Basis for Clinical Response to CTLA-4 Blockade
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CD4 <sup>+</sup> T Cells: Guardians of the Phagosome
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“Although human CD4 T memory cells appear to be long-lived without the eliciting antigen (81), it is difficult to rule out the involvement of periodic TCR stimulation with environmental peptides that cross-react with the eliciting peptide (82).”
BackgroundTissue specific immunity for a changing world
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“Whether TRM can exhibit crossreactivity to newly encountered antigens, as suggested from studies of memory T cells in blood (Su et al., 2013) will be important to define, to assess whether tissue memory can exhibit broad protection.”
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Role of CD4+ T Cells in the Control of Viral Infections: Recent Advances and Open Questions
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“However, improvements in MHC tetramer technology have enabled the detection of rare cells, and shown for instance that the precursor of antiviral CD4+ T cells may acquire a memory phenotype through cross-recognition of environmental or self antigens, thus priming CD4+ T cells for future infections [142,143].”
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Self-citationRetractedProtein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus
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Microbiota and Autoimmunity: Exploring New Avenues
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“Novel approaches involving MHCpeptide tetramers in humans (Su et al., 2013) and mice (Nelson et al.”
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The old friends hypothesis: evolution, immunoregulation and essential microbial inputs
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Revisiting Thymic Positive Selection and the Mature T Cell Repertoire for Antigen
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“This makes apparent what has also been observed empirically (Hemmer et al., 1998; Su et al., 2013): a TCR is able to bind not just a single epitope but a region of ‘‘shape space,’’ such that a protecton contains many more specificities than available self-ligands on which it was selected, and…”
BackgroundStrong homeostatic TCR signals induce formation of self‐tolerant virtual memory CD8 T cells
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“Interestingly, some T cells with an apparent memory phenotype are specific to antigens which the host organism has not been exposed to (Haluszczak et al , 2009; Su et al , 2013).”
InfluentialGao, F., Mallajosyula, V. V. A., Arunachalam, P. S., van der Ploeg, K., Manohar, M., Röltgen, K., Yang, F., Wirz, O. F., Hoh, R. A., Haraguchi, E., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.03.005 · Cited by 87 · see citing works
Self-citationLymphocyte Migration Into Atherosclerotic Plaque
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The T cell antigen receptor: the Swiss army knife of the immune system
Attaf, M., Legut, M., Cole, D. K., & Sewell, A. K. (2015) · Clinical & Experimental Immunology · doi:10.1111/cei.12622 · Cited by 84 · see citing works
- Authors
- Su, L. F., Kidd, B. A., Han, A., Kotzin, J. J., & Davis, M. M.
- Affiliations
- Stanford Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Davis, Mark M.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 38
- Issue
- 2
- Pages
- 373-383
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC3626102
- OpenAlex
- W2060963592
- Cited by
- 429
- References
- 53
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 15 · 2023: 23 · 2022: 26 · 2021: 42 · 2020: 35 · 2019: 29 · 2018: 34 · 2017: 37 · 2016: 32 · 2015: 49 · 2014: 40 · 2013: 39
- FWCI
- 29.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Allergy and Infectious Diseases (U19AI090019, U19AI057229)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007056)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K08AR059760)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CD4+ T cells, memory T cells, T cell receptor cross-reactivity, T cell clonal expansion, HIV-1, influenza, T cell cytokine production, naive T cells, influenza vaccination, microbial peptides, hygiene hypothesis
- MeSH terms
- Adult, Amino Acid Sequence, Child, Clone Cells, Humans, Immunologic Memory, Infant, Newborn, Influenza, Human, Influenza Vaccines, Molecular Sequence Data, Peptides, Phenotype, Receptors, Antigen, T-Cell, Vaccination, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, Immunophenotyping, T-Cell Antigen Receptor Specificity, Cell Proliferation, Influenza A Virus, H1N1 Subtype
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