Thymic Selection Determines γδ T Cell Effector Fate: Antigen-Naive Cells Make Interleukin-17 and Antigen-Experienced Cells Make Interferon γ
Open accessAbstract
gammadelta T cells uniquely contribute to host immune defense, but how this is accomplished remains unclear. Here, we analyzed the nonclassical major histocompatibility complex class I T10 and T22-specific gammadelta T cells in mice and found that encountering antigen in the thymus was neither required nor inhibitory for their development. But when triggered through the T cell receptor, ligand-naive lymphoid-gammadelta T cells produced IL-17, whereas ligand-experienced cells made IFN-gamma. Immediately after immunization, a large fraction of IL-17(+) gammadelta T cells were found in the draining lymph nodes days before the appearance of antigen-specific IL-17(+) *beta T cells. Thus, thymic selection determines the effector fate of gammadelta T cells rather than constrains their antigen specificities. The swift IL-17 response mounted by antigen-naive gammadelta T cells suggests a critical role for these cells at the onset of an acute inflammatory response to novel antigens.
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The cytokine secretion pattern of γδ T cells may vary with antigen exposure.
“the cytokine secretion pattern may vary with antigen exposure [23].”
From The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis (2011) · cites this paper as [23]
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Cites
Th17: An Effector CD4 T Cell Lineage with Regulatory T Cell Ties
Weaver, C. T., Harrington, L. E., Mangan, P. R., Gavrieli, M., & Murphy, K. M. (2006) · Immunity · doi:10.1016/j.immuni.2006.06.002 · Cited by 1,422 · see citing works
Ferrick, D. A., Schrenzel, M. D., Mulvania, T., Hsieh, B., Ferlin, W. G., & Lepper, H. (1995) · Nature · doi:10.1038/373255a0 · Cited by 662 · see citing works
Flagged first, then by citations
Research works printed but not linked: 21
- [1]1. Adams, E.J. ∙ Chien, Y.H. ∙ Garcia, K.C. Structure of a gammadelta T cell receptor in complex with the nonclassical MHC T22 Science. 2005; 308:227-231 Crossref Scopus (204) PubMed Google Scholar
- [2]2. Azzam, H.S. ∙ Grinberg, A. ∙ Lui, K. ... CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity J. Exp. Med. 1998; 188:2301-2311 Crossref Scopus (534) PubMed Google Scholar
- [3]3. Baccala, R. ∙ Witherden, D. ∙ Gonzalez-Quintial, R. ... Gamma delta T cell homeostasis is controlled by IL-7 and IL-15 together with subset-specific factors J. Immunol. 2005; 174:4606-4612 PubMed Google Scholar
- [4]4. Bettelli, E. ∙ Oukka, M. ∙ Kuchroo, V.K. T(H)-17 cells in the circle of immunity and autoimmunity Nat. Immunol. 2007; 8:345-350 Crossref Scopus (1314) PubMed Google Scholar
- [5]5. Bonneville, M. ∙ Ishida, I. ∙ Itohara, S. ... Self-tolerance to transgenic gamma delta T cells by intrathymic inactivation Nature. 1990; 344:163-165 Crossref Scopus (90) PubMed Google Scholar
- [7]7. Crowley, M.P. ∙ Fahrer, A.M. ∙ Baumgarth, N. ... A population of murine gammadelta T cells that recognize an inducible MHC class Ib molecule Science. 2000; 287:314-316 Crossref Scopus (163) PubMed Google Scholar
- [8]8. De Paoli, P. ∙ Gennari, D. ∙ Martelli, P. ... Gamma delta T cell receptor-bearing lymphocytes during Epstein-Barr virus infection J. Infect. Dis. 1990; 161:1013-1016 Crossref Scopus (125) PubMed Google Scholar
- [9]9. Dent, A.L. ∙ Matis, L.A. ∙ Hooshmand, F. ... Self-reactive gamma delta T cells are eliminated in the thymus Nature. 1990; 343:714-719 Crossref Scopus (215) PubMed Google Scholar
- [10]10. Fahrer, A.M. ∙ Konigshofer, Y. ∙ Kerr, E.M. ... Attributes of gammadelta intraepithelial lymphocytes as suggested by their transcriptional profile Proc. Natl. Acad. Sci. USA. 2001; 98:10261-10266 Crossref Scopus (147) PubMed Google Scholar
- [12]12. Forster, R. ∙ Schubel, A. ∙ Breitfeld, D. ... CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs Cell. 1999; 99:23-33 Full Text Full Text (PDF) Scopus (1997) PubMed Google Scholar
- [13]13. French, J.D. ∙ Roark, C.L. ∙ Born, W.K. ... {gamma{delta} T cell homeostasis is established in competition with {alpha}{beta}T cells and NK cells Proc. Natl. Acad. Sci. USA. 2005; 102:14741-14746 Crossref Scopus (55) PubMed Google Scholar
- [14]14. Haks, M.C. ∙ Lefebvre, J.M. ∙ Lauritsen, J.P. ... Attenuation of gammadeltaTCR signaling efficiently diverts thymocytes to the alphabeta lineage Immunity. 2005; 22:595-606 Full Text Full Text (PDF) Scopus (196) PubMed Google Scholar
- [15]15. Hanke, T. ∙ Mitnacht, R. ∙ Boyd, R. ... Induction of interleukin 2 receptor beta chain expression by self-recognition in the thymus J. Exp. Med. 1994; 180:1629-1636 Crossref Scopus (57) PubMed Google Scholar
- [16]16. Havran, W.L. ∙ Allison, J.P. Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors Nature. 1988; 335:443-445 Crossref Scopus (528) PubMed Google Scholar
- [17]17. Havran, W.L. ∙ Chien, Y.H. ∙ Allison, J.P. Recognition of self antigens by skin-derived T cells with invariant gamma delta antigen receptors Science. 1991; 252:1430-1432 Crossref Scopus (354) PubMed Google Scholar
- [18]18. Hayes, S.M. ∙ Li, L. ∙ Love, P.E. TCR signal strength influences alphabeta/gammadelta lineage fate Immunity. 2005; 22:583-593 Full Text Full Text (PDF) Scopus (224) PubMed Google Scholar
- [19]19. Hayes, S.M. ∙ Love, P.E. A retrospective on the requirements for gammadelta T-cell development Immunol. Rev. 2007; 215:8-14 Crossref Scopus (15) PubMed Google Scholar
- [20]20. Hayes, S.M. ∙ Shores, E.W. ∙ Love, P.E. An architectural perspective on signaling by the pre-, alphabeta and gammadelta T cell receptors Immunol. Rev. 2003; 191:28-37 Crossref Scopus (65) PubMed Google Scholar
- [21]21. Ho, M. ∙ Webster, H.K. ∙ Tongtawe, P. ... Increased gamma delta T cells in acute Plasmodium falciparum malaria Immunol. Lett. 1990; 25:139-141 Crossref Scopus (163) PubMed Google Scholar
- [22]22. Huseby, E.S. ∙ White, J. ∙ Crawford, F. ... How the T cell repertoire becomes peptide and MHC specific Cell. 2005; 122:247-260 Full Text Full Text (PDF) Scopus (259) PubMed Google Scholar
- [23]23. Ito, K. ∙ Van Kaer, L. ∙ Bonneville, M. ... Recognition of the product of a novel MHC TL region gene (27b) by a mouse gamma delta T cell receptor Cell. 1990; 62:549-561
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- Authors
- Jensen, K. D. C., Su, X., Shin, S., Li, L., Youssef, S., Yamasaki, S., Steinman, L., Saito, T., Locksley, R. M., Davis, M. M., Baumgarth, N., & Chien, Y.-H.
- Affiliations
- Stanford University (US)
- Howard Hughes Medical Institute (US)
- University of California, Davis (US)
- Corresponding author
- Chien, Yueh-hsiu
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 29
- Issue
- 1
- Pages
- 90-100
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC2601709
- OpenAlex
- W1979530431
- Cited by
- 480
- References
- 2
- Citations by year
- 2026: 14 · 2025: 14 · 2024: 22 · 2023: 21 · 2022: 13 · 2021: 21 · 2020: 29 · 2019: 14 · 2018: 28 · 2017: 26 · 2016: 30 · 2015: 29 · 2014: 29 · 2013: 30 · 2012: 39
- FWCI
- 16.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ScholarlyCommons (University of Pennsylvania) (submittedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service (A1 33431)
- National Institute of Allergy and Infectious Diseases (R01AI033431, U19AI057229)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- γδ T cells, thymic selection, IL-17, interferon-gamma, antigen-experienced T cells, T cell receptor stimulation, acute inflammation, draining lymph nodes
- MeSH terms
- Animals, Antigens, Antigens, Surface, Cell Differentiation, Encephalomyelitis, Autoimmune, Experimental, Flow Cytometry, Interferon-gamma, Lymphocyte Activation, Thymus Gland, Histocompatibility Antigens Class I, T-Lymphocyte Subsets, Receptors, Antigen, T-Cell, gamma-delta, Interleukin-17, Mice
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