Thymic selection determines gammadelta T cell effector fate: antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon gamma.
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.
Jensen
Kirk D C
KD
Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
Su
Xiaoqin
X
Shin
Sunny
S
Li
Luke
L
Youssef
Sawsan
S
Yamasaki
Sho
S
Steinman
Lawrence
L
Saito
Takashi
T
Locksley
Richard M
RM
Davis
Mark M
MM
Baumgarth
Nicole
N
Chien
Yueh-hsiu
YH
D000818:Animals; D000941:Antigens / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis*; D020381:Interleukin-17 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D000941:Antigens; D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; C493536:T10 antigen, mouse; C089395:T22 antigen; D007371:Interferon-gamma