TCR signal strength controls thymic differentiation of discrete proinflammatory gamma-delta T cell subsets
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2016
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Nature Publishing Group
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Muñoz Ruiz, M., Ribot, J. C., Grosso, A. R. et al. «TCR Signal Strength Controls Thymic Differentiation of Discrete Proinflammatory Γδ T Cell Subsets». Nature Immunology, vol. 17, n.o 6, junio de 2016, pp. 721-27. DOI.org (Crossref), https://doi.org/10.1038/ni.3424.
Abstract
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.