%0 Journal Article
%A Muñoz Ruiz, Miguel
%A Ribot, Julie C.
%A Grosso, Ana R.
%A Gonçalves Sousa, Natacha
%A Pamplona, Ana
%A Pennington, Daniel J.
%A Regueiro González-Barros, José Ramón
%A Fernández Malavé, Edgar Gonzalo
%A Silva Santos, Bruno
%T TCR signal strength controls thymic differentiation of discrete proinflammatory gamma-delta T cell subsets
%D 2016
%@ 1529-2908
%U https://hdl.handle.net/20.500.14352/23904
%X The mouse thymus produces discrete gd T cell subsets that make either interferon-g (IFN-g) 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 gd T cells. CD3DH mice had normal numbers and phenotypes of ab thymocyte subsets, but impaired differentiation of fetal Vg6+ (but not Vg4+) IL-17- producing gd T cells and a marked depletion of IFN-g-producing CD122+ NK1.1+ gd T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-g+ gd 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 gd T cell subsets and their impact on pathophysiology.
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