Cutting edge: spontaneous development of IL-17-producing gamma delta T cells in the thymus occurs via a TGF-beta 1-dependent mechanism.
In naive animals, gammadelta T cells are innate sources of IL-17, a potent proinflammatory cytokine mediating bacterial clearance as well as autoimmunity. However, mechanisms underlying the generation of these cells in vivo remain unclear. In this study, we show that TGF-beta1 plays a key role in the generation of IL-17(+) gammadelta T cells and that it mainly occurs in the thymus particularly during the postnatal period. Interestingly, IL-17(+) gammadelta TCR(+) thymocytes were mainly CD44(high)CD25(low) cells, which seem to derive from double-negative 4 gammadelta TCR(+) cells that acquired CD44 and IL-17 expression. Our findings identify a novel developmental pathway during which IL-17-competent gammadelta T cells arise in the thymus by a TGF-beta1-dependent mechanism.
Do
Jeong-su
JS
Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Fink
Pamela J
PJ
Li
Lily
L
Spolski
Rosanne
R
Robinson
Janet
J
Leonard
Warren J
WJ
Letterio
John J
JJ
Min
Booki
B
D000818:Animals; D000831:Animals, Newborn; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis*; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018125:Receptors, Transforming Growth Factor beta; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1