TCR signal strength controls thymic differentiation of discrete proinflammatory ?? T cell subsets.

ABSTRACT: The mouse thymus produces discrete ?? T cell subsets that make either interferon-? (IFN-?) 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 ?? T cells. CD3DH mice had normal numbers and phenotypes of ?? thymocyte subsets, but impaired differentiation of fetal V?6(+) (but not V?4(+)) IL-17-producing ?? T cells and a marked depletion of IFN-?-producing CD122(+) NK1.1(+) ?? T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-?(+) ?? 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 ?? T cell subsets and their impact on pathophysiology.

SUBMITTER: Munoz-Ruiz M 

PROVIDER: S-EPMC4875770 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature