The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Skin-resident memory CD4+ T cells enhance protection against Leishmania major infection
Open accessAbstract
Leishmaniasis causes a significant disease burden worldwide. Although Leishmania-infected patients become refractory to reinfection after disease resolution, effective immune protection has not yet been achieved by human vaccines. Although circulating Leishmania-specific T cells are known to play a critical role in immunity, the role of memory T cells present in peripheral tissues has not been explored. Here, we identify a population of skin-resident Leishmania-specific memory CD4+ T cells. These cells produce IFN-γ and remain resident in the skin when transplanted by skin graft onto naive mice. They function to recruit circulating T cells to the skin in a CXCR3-dependent manner, resulting in better control of the parasites. Our findings are the first to demonstrate that CD4+ TRM cells form in response to a parasitic infection, and indicate that optimal protective immunity to Leishmania, and thus the success of a vaccine, may depend on generating both circulating and skin-resident memory T cells.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Th17 cells play a critical role in host defense against C. albicans [30–33,36], whereas Th1 cells protect the host against reinfection from HSV and L. major [34,35].”
From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [35]
The cited source says what the claim attributes to it.
In the citing paper
“Effector T cells play a critical role in the host’s defense during reinfection with C. albicans, Staphylococcus aureus, Leishmania major, and HSV [28,30–35].”
From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [35]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Furthermore, previous findings from our laboratory [16] and others [35] suggest that other cell types, such as keratinocytes and NK cells, also express IL-17A and IFNγ, respectively.”
From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [35]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Preferential Localization of Effector Memory Cells in Nonlymphoid Tissue
Masopust, D., Vezys, V., Marzo, A. L., & Lefrançois, L. (2001) · Science · doi:10.1126/science.1058867 · Cited by 1,952 · cited 2×
“In addition to circulating memory T cells, an additional memory T cell subset resides in the tissues as resident memory T cells (TRM; Kim et al., 1999; Hogan et al., 2001a; Masopust et al., 2001; Clark et al., 2006; Gebhardt et al., 2009; Wakim et al., 2010; Hofmann and Pircher, 2011; Jiang et al., 2012; Mackay et al.…”
BackgroundCD4+CD25+ regulatory T cells control Leishmania major persistence and immunity
Belkaid, Y., Piccirillo, C. A., Méndez, S., Shevach, E. M., & Sacks, D. L. (2002) · Nature · doi:10.1038/nature01152 · Cited by 1,726
Gebhardt, T., Wakim, L. M., Eidsmo, L., Reading, P. C., Heath, W. R., & Carbone, F. R. (2009) · Nature Immunology · doi:10.1038/ni.1718 · Cited by 1,157
Skin infection generates non-migratory memory CD8+ TRM cells providing global skin immunity
Jiang, X., Clark, R. A., Liu, L., Wagers, A. J., Fuhlbrigge, R. C., & Kupper, T. S. (2012) · Nature · doi:10.1038/nature10851 · Cited by 883
Dutton, R. W., Bradley, L. M., & Swain, S. L. (1998) · Annual Review of Immunology · doi:10.1146/annurev.immunol.16.1.201 · Cited by 832
The Vast Majority of CLA+ T Cells Are Resident in Normal Skin
Clark, R. A., Chong, B., Mirchandani, N., Brinster, N. K., Yamanaka, K.-I., Dowgiert, R. K., & Kupper, T. S. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.7.4431 · Cited by 796
Resident memory CD8 T cells trigger protective innate and adaptive immune responses
Schenkel, J. M., Fraser, K. A., Beura, L. K., Pauken, K. E., Vezys, V., & Masopust, D. (2014) · Science · doi:10.1126/science.1254536 · Cited by 731
Sensing and alarm function of resident memory CD8+ T cells
Schenkel, J., Fraser, K. A., Vezys, V., & Masopust, D. (2013) · Nature Immunology · doi:10.1038/ni.2568 · Cited by 648
Teijaro, J. R., Turner, D., Pham, Q., Wherry, E. J., Lefrançois, L., & Farber, D. L. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1102243 · Cited by 641
Mackay, L. K., Stock, A. T., Ma, J., Jones, C. M., Kent, S., Mueller, S. N., Heath, W., Carbone, F., & Gebhardt, T. (2012) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1202288109 · Cited by 638
Wakim, L. M., Davis, A. S. W., & Bevan, M. J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010201107 · Cited by 586
Watanabe, R., Gehad, A., Yang, C., Scott, L. L., Teague, J. E., Schlapbach, C., Elco, C. P., Huang, V., Matos, T. R., Kupper, T. S., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.3010302 · Cited by 569
CD8+ T lymphocyte mobilization to virus-infected tissue requires CD4+ T-cell help
Nakanishi, Y., Lu, B., Gerard, C. J., & Iwasaki, A. (2009) · Nature · doi:10.1038/nature08511 · Cited by 567
Skin-resident memory CD8 + T cells trigger a state of tissue-wide pathogen alert
Ariotti, S., Hogenbirk, M. A., Dijkgraaf, F. E., Visser, L. L., Hoekstra, M. E., Song, J., Jacobs, H., Haanen, J. B. A. G., & Schumacher, T. N. (2014) · Science · doi:10.1126/science.1254803 · Cited by 534
A local macrophage chemokine network sustains protective tissue-resident memory CD4 T cells
Iijima, N., & Iwasaki, A. (2014) · Science · doi:10.1126/science.1257530 · Cited by 420
Hogan, R. J., Usherwood, E. J., Zhong, W., Roberts, A. D., Dutton, R. W., Harmsen, A. G., & Woodland, D. L. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.3.1813 · Cited by 409
Laidlaw, B. J., Zhang, N., Marshall, H. D., Staron, M. M., Guan, T., Hu, Y., Cauley, L. S., Craft, J. E., & Kaech, S. M. (2014) · Immunity · doi:10.1016/j.immuni.2014.09.007 · Cited by 382
Späth, G. F., & Beverley, S. M. (2001) · Experimental Parasitology · doi:10.1006/expr.2001.4656 · Cited by 376
Clark, R. A., Watanabe, R., Teague, J. E., Schlapbach, C., Tawa, M. C., Adams, N., Dorosario, A. A., Chaney, K. S., Cutler, C. S., LeBoeuf, N. R., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003008 · Cited by 367
Zaph, C., Uzonna, J. E., Beverley, S. M., & Scott, P. (2004) · Nature Medicine · doi:10.1038/nm1108 · Cited by 348
Self-citationIntravascular staining redefines lung CD8 T cell responses
Anderson, K., Sung, H., Skon, C. N., Lefrançois, L., Deisinger, A., Vezys, V., & Masopust, D. (2012) · Journal of Immunology · doi:10.4049/jimmunol.1201682 · Cited by 309
Méndez, S., Reckling, S. K., Piccirillo, C. A., Sacks, D. L., & Belkaid, Y. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040298 · Cited by 296
Memory CD4 T cells emerge from effector T-cell progenitors
Harrington, L., Janowski, K., Oliver, J., Zajac, A., & Weaver, C. (2008) · Nature · doi:10.1038/nature06672 · Cited by 290
Self-citationHogan, R. J., Zhong, W., Usherwood, E. J., Cookenham, T. S., Roberts, A. D., & Woodland, D. L. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.8.981 · Cited by 288
Second-generation vaccines against leishmaniasis
Coler, R., & Reed, J. (2005) · Trends in Parasitology · doi:10.1016/j.pt.2005.03.006 · Cited by 270
First generation leishmaniasis vaccines: A review of field efficacy trials
Noazin, S., Modabber, F. Z., Khamesipour, A., Smith, P. G., Moulton, L. H., Nasseri, K., Sharifi, I., Khalil, E. A. G., Vélez, I. D., Antunes, C., et al. (2008) · Vaccine · doi:10.1016/j.vaccine.2008.09.085 · Cited by 185
Leishmaniavaccines: progress and problems
Kedzierski, Ł., Zhu, Y., & Handman, E. (2006) · Parasitology · doi:10.1017/s0031182006001831 · Cited by 182
Uzonna, J. E., Wei, G., Yurkowski, D. P., & Bretscher, P. A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.12.6967 · Cited by 182
E-cadherin promotes accumulation of a unique memory CD8 T-cell population in murine salivary glands
Hofmann, M., & Pircher, H. (2011) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1107200108 · Cited by 173
Bromley, S. K., Yan, S., Tomura, M., Kanagawa, O., & Luster, A. D. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1202805 · Cited by 173
Induction and Visualization of Mucosal Memory CD8 T Cells Following Systemic Virus Infection
Kim, S.-K., Schluns, K. S., & Lefrançois, L. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.8.4125 · Cited by 145
Scott, P., Artis, D., Uzonna, J. E., & Zaph, C. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.00198.x · Cited by 133
Self-citationPeters, N. C., Pagán, A. J., Lawyer, P. G., Hand, T. W., Roma, E. H., Stamper, L., Romano, A., & Sacks, D. L. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004538 · Cited by 92
Vaccines for Canine Leishmaniasis
Palatnik, M. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00069 · Cited by 89
Uppaluri, R., Sheehan, K. C. F., Wang, L., Bui, J. D., Brotman, J. J., Lu, B., Gerard, C. J., Hancock, W. W., & Schreiber, R. D. (2008) · Transplantation · doi:10.1097/tp.0b013e31817b8e4b · Cited by 77
Colpitts, S. L., Dalton, N. M., & Scott, P. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803450 · Cited by 76
Self-citationVaccines against tropical parasitic diseases: a persisting answer to a persisting problem
Sacks, D. L. (2014) · Nature Immunology · doi:10.1038/ni.2853 · Cited by 70
Leishmania vaccines: from leishmanization to the era of DNA technology
Dunning, N. L. (2009) · Bioscience Horizons The International Journal of Student Research · doi:10.1093/biohorizons/hzp004 · Cited by 54
Chao, N. J. A. (2007) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2007.10.013 · Cited by 42
The early generation of a heterogeneous CD4+ T cell response to Leishmania major
Colpitts, S. L., & Scott, P. (2010) · Journal of Immunology · doi:10.4049/jimmunol.1000483 · Cited by 32
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Human T cell development, localization, and function throughout life
Kumar, B. V., Connors, T. J., & Farber, D. L. (2018) · Immunity · doi:10.1016/j.immuni.2018.01.007 · Cited by 1,257
Tissue-resident memory T cells: local specialists in immune defence
Mueller, S. N., & Mackay, L. K. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2015.3 · Cited by 1,006
CD49a Expression Defines Tissue-Resident CD8 + T Cells Poised for Cytotoxic Function in Human Skin
Cheuk, S., Schlums, H., Gallais Sérézal, I., Martini, E., Chiang, S. C., Marquardt, N., Gibbs, A., Detlofsson, E., Introini, A., Forkel, M., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.01.009 · Cited by 678
The multifaceted role of CD4+ T cells in CD8+ T cell memory
Laidlaw, B. J., Craft, J. E., & Kaech, S. M. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2015.10 · Cited by 657
Tissue-Resident T Cells and Other Resident Leukocytes
Masopust, D., & Soerens, A. G. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053214 · Cited by 608
Metadata
- Authors
- Glennie, N. D., Yeramilli, V. A., Beiting, D. P., Volk, S. W., Weaver, C. T., & Scott, P.
- Affiliations
- University of Pennsylvania (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Scott, Phillip
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2015-07-27
- Volume
- 212
- Issue
- 9
- Pages
- 1405-1414
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC4548053
- OpenAlex
- W2162538566
- Cited by
- 204
- References
- 41
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 12 · 2023: 14 · 2022: 14 · 2021: 29 · 2020: 21 · 2019: 21 · 2018: 26 · 2017: 22 · 2016: 20 · 2015: 5
- FWCI
- 26.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R21AI110869, T32AI007532)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- Leishmania major, cutaneous leishmaniasis, skin-resident memory T cells, CD4+ T cells, interferon-gamma, CXCR3, skin grafting, protective immunity, leishmaniasis vaccine, parasite control
- MeSH terms
- Animals, Humans, Immunologic Memory, Interferon-gamma, Mice, Transgenic, Skin, CD4-Positive T-Lymphocytes, Leishmaniasis, Cutaneous, Leishmania major, Mice, Receptors, CXCR3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
