| First Author | Muñoz-Ruiz M | Year | 2016 |
| Journal | Nat Immunol | Volume | 17 |
| Issue | 6 | Pages | 721-727 |
| PubMed ID | 27043412 | Mgi Jnum | J:259151 |
| Mgi Id | MGI:6142492 | Doi | 10.1038/ni.3424 |
| Citation | Munoz-Ruiz M, et al. (2016) TCR signal strength controls thymic differentiation of discrete proinflammatory gammadelta T cell subsets. Nat Immunol 17(6):721-727 |
| abstractText | The mouse thymus produces discrete gammadelta T cell subsets that make either interferon-gamma (IFN-gamma) or interleukin 17 (IL-17), but the role of the T cell antigen receptor (TCR) in this developmental process remains controversial. Here we show that Cd3g(+/-) Cd3d(+/-) (CD3 double-haploinsufficient (CD3DH)) mice have reduced TCR expression and signaling strength on gammadelta T cells. CD3DH mice had normal numbers and phenotypes of alphabeta thymocyte subsets, but impaired differentiation of fetal Vgamma6(+) (but not Vgamma4(+)) IL-17-producing gammadelta T cells and a marked depletion of IFN-gamma-producing CD122(+) NK1.1(+) gammadelta T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-gamma(+) gammadelta T cells and were resistant to experimental cerebral malaria. Thus, TCR signal strength within specific thymic developmental windows is a major determinant of the generation of proinflammatory gammadelta T cell subsets and their impact on pathophysiology. |
