CoChat
Sign Up
Cited by 21T-cell and B-cell ImmunologyImmune responses and vaccinationsImmunotherapy and Immune Responses

Diverse CD8 T Cell Responses to Viral Infection Revealed by the Collaborative Cross

Open access
Martin, Matthew D., Sompallae, Ramakrishna, Winborn, Christina S., Harty, John T., Badovinac, Vladimir P.·2020·Cell Reports
DOI 10.1016/j.celrep.2020.03.072PMC PMC7212788
Open this paper in CoChat — free accountOpen PDF

Abstract

Enhanced host protection against re-infection requires generation of memory T cells of sufficient quantity and functional quality. Unlike well-studied inbred mice, T cell responses of diverse size and quality are generated following infection of humans and outbred mice. Thus, additional models are needed that accurately reflect variation in immune outcomes in genetically diverse populations and to uncover underlying genetic causes. The Collaborative Cross (CC), a large recombinant inbred panel of mice, is an ideal model in this pursuit for the high degree of genetic variation present, because it allows for assessment of genetic factors underlying unique phenotypes. Here, we advance the utility of the CC as a tool to analyze the immune response to viral infection. We describe variability in resting immune cell composition and adaptive immune responses generated among CC strains following systemic virus infection and reveal quantitative trait loci responsible for generation of CD62L+ memory CD8 T cells.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.celrep.2020.03.072

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

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.

A few free checks a day · papers already verified open instantly · results are public

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 63

  1. Bachmann MF, Wolint P, Schwarz K, Jäger P, and Oxenius A (2005). Functional properties and lineage relationship of CD8+ T cell subsets identified by expression of IL-7 receptor alpha and CD62L. J. Immunol 175, 4686– 4696. 16177116
  2. Beura LK, Hamilton SE, Bi K, Schenkel JM, Odumade OA, Casey KA, Thompson EA, Fraser KA, Rosato PC, Filali-Mouhim A, (2016). Normalizing the environment recapitulates adult human immune traits in laboratory mice. Nature 532, 512– 516. 27096360 PMC4871315
  3. Brown LE, and Kelso A (2009). Prospects for an influenza vaccine that induces cross-protective cytotoxic T lymphocytes. Immunol. Cell Biol 87, 300– 308. 19308073
  4. Busch DH, Kerksiek KM, and Pamer EG (2000). Differing roles of inflammation and antigen in T cell proliferation and memory generation. J. Immunol 164, 4063– 4070. 10754299
  5. Chesler EJ, Miller DR, Branstetter LR, Galloway LD, Jackson BL, Philip VM, Voy BH, Culiat CT, Threadgill DW, Williams RW, (2008). The Collaborative Cross at Oak Ridge National Laboratory: developing a powerful resource for systems genetics. Mamm. Genome 19, 382– 389. 18716833 PMC2745091
  6. Churchill GA, Airey DC, Allayee H, Angel JM, Attie AD, Beatty J, Beavis WD, Belknap JK, Bennett B, Berrettini W,; Complex Trait Consortium (2004). The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat. Genet 36, 1133– 1137. 15514660
  7. Collaborative Cross Consortium (2012). The genome architecture of the Collaborative Cross mouse genetic reference population. Genetics 190, 389– 401. 22345608 PMC3276630
  8. Collin R, Balmer L, Morahan G, and Lesage S (2019). Common heritable immunological variations revealed in genetically diverse inbred mouse strains of the Collaborative Cross. J. Immunol 202, 777– 786. 30587532
  9. Cook PC, Owen H, Deaton AM, Borger JG, Brown SL, Clouaire T, Jones GR, Jones LH, Lundie RJ, Marley AK, (2015). A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells. Nat. Commun 6, 6920. 25908537 PMC4413429
  10. Crotty S (2015). A brief history of T cell help to B cells. Nat. Rev. Immunol 15, 185– 189. 25677493 PMC4414089
  11. Curtsinger JM, Valenzuela JO, Agarwal P, Lins D, and Mescher MF (2005). Type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation. J. Immunol 174, 4465– 4469. 15814665
  12. Duan S, and Thomas PG (2016). Balancing immune protection and immune pathology by CD8(+) T-cell responses to influenza infection. Front. Immunol 7, 25. 26904022 PMC4742794
  13. DuPage M, and Bluestone JA (2016). Harnessing the plasticity of CD4(+) T cells to treat immune-mediated disease. Nat. Rev. Immunol 16, 149– 163. 26875830
  14. Eberlein J, Davenport B, Nguyen T, Victorino F, Haist K, Jhun K, Karimpour-Fard A, Hunter L, Kedl R, Clambey ET, and Homann D (2016). Aging promotes acquisition of naive-like CD8+ memory T cell traits and enhanced functionalities. J. Clin. Invest 126, 3942– 3960. 27617858 PMC5096808
  15. Elbahesh H, and Schughart K (2016). Genetically diverse CC-founder mouse strains replicate the human influenza gene expression signature. Sci. Rep 6, 26437. 27193691 PMC4872221
  16. Epstein JE, Tewari K, Lyke KE, Sim BK, Billingsley PF, Laurens MB, Gunasekera A, Chakravarty S, James ER, Sedegah M, (2011). Live attenuated malaria vaccine designed to protect through hepatic CD8+ T cell immunity. Science 334, 475– 480. 21903775
  17. Ferris MT, Aylor DL, Bottomly D, Whitmore AC, Aicher LD, Bell TA, Bradel-Tretheway B, Bryan JT, Buus RJ, Gralinski LE, (2013). Modeling host genetic regulation of influenza pathogenesis in the collaborative cross. PLoS Pathog. 9, e1003196. 23468633 PMC3585141
  18. Gatti DM, Svenson KL, Shabalin A, Wu LY, Valdar W, Simecek P, Goodwin N, Cheng R, Pomp D, Palmer A, (2014). Quantitative trait locus mapping methods for diversity outbred mice. G3 (Bethesda) 4, 1623– 1633. 25237114 PMC4169154
  19. Gerlach C, Moseman EA, Loughhead SM, Alvarez D, Zwijnenburg AJ, Waanders L, Garg R, de la Torre JC, and von Andrian UH (2016). The chemokine receptor CX3CR1 defines three antigen-experienced CD8 T cell subsets with distinct roles in immune surveillance and homeostasis. Immunity 45, 1270– 1284. 27939671 PMC5177508
  20. Graham JB, Thomas S, Swarts J, McMillan AA, Ferris MT, Suthar MS, Treuting PM, Ireton R, Gale M Jr., and Lund JM (2015). Genetic diversity in the collaborative cross model recapitulates human West Nile virus disease outcomes. MBio 6, e00493– 15. 25944860 PMC4436067
  21. Graham JB, Swarts JL, Wilkins C, Thomas S, Green R, Sekine A, Voss KM, Ireton RC, Mooney M, Choonoo G, (2016). A mouse model of chronic West Nile virus disease. PLoS Pathog. 12, e1005996. 27806117 PMC5091767
  22. Graham JB, Swarts JL, Mooney M, Choonoo G, Jeng S, Miller DR, Ferris MT, McWeeney S, and Lund JM (2017). Extensive homeostatic T cell phenotypic variation within the Collaborative Cross. Cell Rep. 21, 2313– 2325. 29166619 PMC5728448
  23. Gralinski LE, Ferris MT, Aylor DL, Whitmore AC, Green R, Frieman MB, Deming D, Menachery VD, Miller DR, Buus RJ, (2015). Genome wide identification of SARS-CoV susceptibility loci using the Collaborative Cross. PLoS Genet. 11, e1005504. 26452100 PMC4599853
  24. Iraqi FA, Churchill G, and Mott R (2008). The Collaborative Cross, developing a resource for mammalian systems genetics: a status report of the Well-come Trust cohort. Mamm. Genome 19, 379– 381. 18521666
  25. Jia A, Wang Y, Sun W, Xiao B, Wei Y, Qiu L, Mu L, Xu L, Li J, Zhang X, (2017). MBD2 regulates Th17 cell differentiation and experimental severe asthma by affecting IRF4 expression. Mediators Inflamm. 2017, 6249685. 28808358 PMC5541825
  26. Joshi NS, Cui W, Chandele A, Lee HK, Urso DR, Hagman J, Gapin L, and Kaech SM (2007). Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor. Immunity 27, 281– 295. 17723218 PMC2034442
  27. Laidlaw BJ, Craft JE, and Kaech SM (2016). The multifaceted role of CD4(+) T cells in CD8(+) T cell memory. Nat. Rev. Immunol 16, 102– 111. 26781939 PMC4860014
  28. Lapo sová K, Pastoreková S, and Tomá sková J (2013). Lymphocytic choriomeningitis virus: invisible but not innocent. Acta Virol. 57, 160– 170. 23600874
  29. Leist SR, Pilzner C, van den Brand JM, Dengler L, Geffers R, Kuiken T, Balling R, Kollmus H, and Schughart K (2016). Influenza H3N2 infection of the collaborative cross founder strains reveals highly divergent host responses and identifies a unique phenotype in CAST/EiJ mice. BMC Genomics 17, 143. 26921172 PMC4769537
  30. Lorè NI, Iraqi FA, and Bragonzi A (2015). Host genetic diversity influences the severity of Pseudomonas aeruginosa pneumonia in the Collaborative Cross mice. BMC Genet. 16, 106. 26310945 PMC4551369
  31. Mackay LK, and Kallies A (2017). Transcriptional regulation of tissue-resident lymphocytes. Trends Immunol. 38, 94– 103. 27939451
  32. Mackay LK, Stock AT, Ma JZ, Jones CM, Kent SJ, Mueller SN, Heath WR, Carbone FR, and Gebhardt T (2012). Long-lived epithelial immunity by tissue-resident memory T (TRM) cells in the absence of persisting local antigen presentation. Proc. Natl. Acad. Sci. USA 109, 7037– 7042. 22509047 PMC3344960
  33. Martin MD, Kim MT, Shan Q, Sompallae R, Xue HH, Harty JT, and Badovinac VP (2015). Phenotypic and functional alterations in circulating memory CD8 T cells with time after primary infection. PLoS Pathog. 11, e1005219. 26485703 PMC4618693
  34. Martin MD, Danahy DB, Hartwig SM, Harty JT, and Badovinac VP (2017). Revealing the complexity in CD8 T cell responses to infection in inbred C57B/6 versus outbred Swiss mice. Front. Immunol 8, 1527. 29213267 PMC5702636
  35. Masopust D (2009). Developing an HIV cytotoxic T-lymphocyte vaccine: issues of CD8 T-cell quantity, quality and location. J. Intern. Med 265, 125– 137. 19093965
  36. Masopust D, Sivula CP, and Jameson SC (2017). Of mice, dirty mice, and men: using mice to understand human immunology. J. Immunol 199, 383– 388. 28696328 PMC5512602
  37. McDermott DS, and Varga SM (2011). Quantifying antigen-specific CD4 T cells during a viral infection: CD4 T cell responses are larger than we think. J. Immunol 187, 5568– 5576. 22043009 PMC3221938
  38. Morahan G, Balmer L, and Monley D (2008). Establishment of “The Gene Mine”: a resource for rapid identification of complex trait genes. Mamm. Genome 19, 390– 393. 18716834
  39. Nolz JC, and Harty JT (2011). Protective capacity of memory CD8+ T cells is dictated by antigen exposure history and nature of the infection. Immunity 34, 781– 793. 21549619 PMC3103642
  40. Olson JA, McDonald-Hyman C, Jameson SC, and Hamilton SE (2013). Effector-like CD8+ T cells in the memory population mediate potent protective immunity. Immunity 38, 1250– 1260. 23746652 PMC3703254
  41. Pamer EG (2004). Immune responses to Listeria monocytogenes. Nat. Rev. Immunol 4, 812– 823. 15459672
  42. Pham NL, Badovinac VP, and Harty JT (2009). A default pathway of memory CD8 T cell differentiation after dendritic cell immunization is deflected by encounter with inflammatory cytokines during antigen-driven proliferation. J. Immunol 183, 2337– 2348. 19635915 PMC2786780
  43. Phillippi J, Xie Y, Miller DR, Bell TA, Zhang Z, Lenarcic AB, Aylor DL, Krovi SH, Threadgill DW, de Villena FP, (2014). Using the emerging Collaborative Cross to probe the immune system. Genes Immun. 15, 38– 46. 24195963 PMC4004367
  44. Porter BB, and Harty JT (2006). The onset of CD8+-T-cell contraction is influenced by the peak of Listeria monocytogenes infection and antigen display. Infect. Immun 74, 1528– 1536. 16495523 PMC1418632
  45. Rai D, Pham NL, Harty JT, and Badovinac VP (2009). Tracking the total CD8 T cell response to infection reveals substantial discordance in magnitude and kinetics between inbred and outbred hosts. J. Immunol 183, 7672– 7681. 19933864 PMC2808048
  46. Reese TA, Bi K, Kambal A, Filali-Mouhim A, Beura LK, Bürger MC, Pulendran B, Sekaly RP, Jameson SC, Masopust D, (2016). Sequential infection with common pathogens promotes human-like immune gene expression and altered vaccine response. Cell Host Microbe 19, 713– 719. 27107939 PMC4896745
  47. Sahin U, Derhovanessian E, Miller M, Kloke BP, Simon P, Löwer M, Bukur V, Tadmor AD, Luxemburger U, Schrörs B, (2017). Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547, 222– 226. 28678784
  48. Sallusto F, Lenig D, Förster R, Lipp M, and Lanzavecchia A (1999). Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401, 708– 712. 10537110
  49. Schenkel JM, Fraser KA, Vezys V, and Masopust D (2013). Sensing and alarm function of resident memory CD8+ T cells. Nat. Immunol 14, 509– 513. 23542740 PMC3631432
  50. Schmidt ME, and Varga SM (2018). The CD8 T cell response to respiratory virus infections. Front. Immunol 9, 678. 29686673 PMC5900024
  51. Schmidt NW, Podyminogin RL, Butler NS, Badovinac VP, Tucker BJ, Bahjat KS, Lauer P, Reyes-Sandoval A, Hutchings CL, Moore AC, (2008). Memory CD8 T cell responses exceeding a large but definable threshold provide long-term immunity to malaria. Proc. Natl. Acad. Sci. USA 105, 14017– 14022. 18780790 PMC2544571
  52. Schmidt NW, Butler NS, Badovinac VP, and Harty JT (2010). Extreme CD8 T cell requirements for anti-malarial liver-stage immunity following immunization with radiation attenuated sporozoites. PLoS Pathog. 6, e1000998. 20657824 PMC2904779
  53. Seder RA, Chang LJ, Enama ME, Zephir KL, Sarwar UN, Gordon IJ, Holman LA, James ER, Billingsley PF, Gunasekera A,; VRC 312 Study Team (2013). Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science 341, 1359– 1365. 23929949
  54. Slütter B, Pewe LL, Kaech SM, and Harty JT (2013). Lung airway-surveilling CXCR3(hi) memory CD8(+) T cells are critical for protection against influenza A virus. Immunity 39, 939– 948. 24238342 PMC3872058
  55. Slütter B, Van Braeckel-Budimir N, Abboud G, Varga SM, Salek-Ardakani S, and Harty JT (2017). Dynamics of influenza-induced lung-resident memory T cells underlie waning heterosubtypic immunity. Sci. Immunol 2, eaag2031. 28783666 PMC5590757
  56. Srivastava A, Morgan AP, Najarian ML, Sarsani VK, Sigmon JS, Shorter JR, Kashfeen A, McMullan RC, Williams LH, Giusti-Rodríguez P, (2017). Genomes of the mouse Collaborative Cross. Genetics 206, 537– 556. 28592495 PMC5499171
  57. Threadgill DW, and Churchill GA (2012). Ten years of the collaborative cross. G3 (Bethesda) 2, 153– 156. 22384393 PMC3284322
  58. Threadgill DW, Miller DR, Churchill GA, and de Villena FP (2011). The collaborative cross: a recombinant inbred mouse population for the systems genetic era. ILAR J. 52, 24– 31. 21411855
  59. Welsh CE, Miller DR, Manly KF, Wang J, McMillan L, Morahan G, Mott R, Iraqi FA, Threadgill DW, and de Villena FP (2012). Status and access to the Collaborative Cross population. Mamm. Genome 23, 706– 712. 22847377 PMC3463789
  60. Wherry EJ, Teichgräber V, Becker TC, Masopust D, Kaech SM, Antia R, von Andrian UH, and Ahmed R (2003). Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat. Immunol 4, 225– 234. 12563257
  61. Wirth TC, Harty JT, and Badovinac VP (2010). Modulating numbers and phenotype of CD8+ T cells in secondary immune responses. Eur. J. Immunol 40, 1916– 1926. 20411564 PMC2993099
  62. Wu T, Hu Y, Lee YT, Bouchard KR, Benechet A, Khanna K, and Cauley LS (2014). Lung-resident memory CD8 T cells (TRM) are indispensable for optimal cross-protection against pulmonary virus infection. J. Leukoc. Biol 95, 215– 224. 24006506 PMC3896663
  63. Zhou X, Ramachandran S, Mann M, and Popkin DL (2012). Role of lymphocytic choriomeningitis virus (LCMV) in understanding viral immunology: past, present and future. Viruses 4, 2650– 2669. 23202498 PMC3509666

Cited by

Sorted by citations

Authors
Martin, M. D., Sompallae, R., Winborn, C. S., Harty, J. T., & Badovinac, V. P.
Affiliations
University of Iowa (US)
Corresponding author
Badovinac, Vladimir P.
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2020-04
Volume
31
Issue
2
Pages
107508
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2020.03.072
PMC
PMC7212788
OpenAlex
W3015403097
Cited by
21
References
2
Citations by year
2026: 3 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 4
FWCI
1.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
Funders
National Institutes of Health (AI100527, AI114543, AI147064, AI42767, AI85515, GM113961, GM134880)
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
CD8+ T cells, Collaborative Cross, viral infection, memory T cells, quantitative trait loci, genetic diversity, recombinant inbred mouse strains, L-selectin, immune response variability, adaptive immunity
MeSH terms
Animals, Crosses, Genetic, Female, Genotype, Haplotypes, Immunologic Memory, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred Strains, Phenotype, T-Lymphocytes, Genetic Variation, Virus Diseases, CD8-Positive T-Lymphocytes, Models, Immunological, Quantitative Trait Loci, Mice

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