TY - JOUR
T1 - Thymic Selection Determines γδ T Cell Effector Fate
T2 - Antigen-Naive Cells Make Interleukin-17 and Antigen-Experienced Cells Make Interferon γ
AU - Jensen, Kirk D.C.
AU - Su, Xiaoqin
AU - Shin, Sunny
AU - Li, Luke
AU - Youssef, Sawsan
AU - Yamasaki, Sho
AU - Steinman, Lawrence
AU - Saito, Takashi
AU - Locksley, Richard M.
AU - Davis, Mark M.
AU - Baumgarth, Nicole
AU - Chien, Yueh hsiu
N1 - Funding Information:
We thank J. Cyster (UCSF) for the anti-S1P 1 polyclonal rabbit serum, E. Gallo and G. Crabtree for the use of CSA-treated β 2 m, MHC II null mice, the 197G2 antibody, and for discussions regarding its use, C. Franco for assistance with cloning, L. Reinhardt for facilitating experiments with YETI mice, and Y. Konigshofer for comments. Author contributions are as follows: K.J., X.S., S.S., and Y.C. designed experiments; K.J., X.S., S.S., L.L., and Sa.Y. performed experiments; Sho.Y. and T.S. provided reagents and advice on the EPOR-BAF3 experiments; L.S. provided advice on the MOG-CFA inflammatory response model; N.B. performed qPCR analysis on IELs; R.L. provided YETI mice and advice; K.J., X.S., S.S., and Y.C. analyzed the results; and K.J., L.L., M.M.D., and Y.C. wrote the paper. K.J. was supported by the Stanford Graduate Fellowship and the National Institutes of Health (NIH) Cell and Molecular Biology (CMB) training grant. This work was supported by NIH grants A1 33431 and U19 AI 057229 (Y.C.).
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/7/18
Y1 - 2008/7/18
N2 - γδ 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 γδ 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-γδ T cells produced IL-17, whereas ligand-experienced cells made IFN-γ. Immediately after immunization, a large fraction of IL-17+ γδ T cells were found in the draining lymph nodes days before the appearance of antigen-specific IL-17+ αβ T cells. Thus, thymic selection determines the effector fate of γδ T cells rather than constrains their antigen specificities. The swift IL-17 response mounted by antigen-naive γδ T cells suggests a critical role for these cells at the onset of an acute inflammatory response to novel antigens.
AB - γδ 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 γδ 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-γδ T cells produced IL-17, whereas ligand-experienced cells made IFN-γ. Immediately after immunization, a large fraction of IL-17+ γδ T cells were found in the draining lymph nodes days before the appearance of antigen-specific IL-17+ αβ T cells. Thus, thymic selection determines the effector fate of γδ T cells rather than constrains their antigen specificities. The swift IL-17 response mounted by antigen-naive γδ T cells suggests a critical role for these cells at the onset of an acute inflammatory response to novel antigens.
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U2 - 10.1016/j.immuni.2008.04.022
DO - 10.1016/j.immuni.2008.04.022
M3 - Article
C2 - 18585064
AN - SCOPUS:46749113368
VL - 29
SP - 90
EP - 100
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 1
ER -