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Publication : Pro-inflammatory self-reactive T cells are found within murine TCR-αβ(+) CD4(-) CD8(-) PD-1(+) cells.

First Author  Rodríguez-Rodríguez N Year  2016
Journal  Eur J Immunol Volume  46
Issue  6 Pages  1383-91
PubMed ID  27060346 Mgi Jnum  J:246253
Mgi Id  MGI:5923629 Doi  10.1002/eji.201546056
Citation  Rodriguez-Rodriguez N, et al. (2016) Pro-inflammatory self-reactive T cells are found within murine TCR-alphabeta(+) CD4(-) CD8(-) PD-1(+) cells. Eur J Immunol 46(6):1383-91
abstractText  TCR-alphabeta(+) double negative (DN) T cells (CD3(+) TCR-alphabeta(+) CD4(-) CD8(-) NK1.1(-) CD49b(-) ) represent a minor heterogeneous population in healthy humans and mice. These cells have been ascribed pro-inflammatory and regulatory capacities and are known to expand during the course of several autoimmune diseases. Importantly, previous studies have shown that self-reactive CD8(+) T cells become DN after activation by self-antigens, suggesting that self-reactive T cells may exist within the DN T-cell population. Here, we demonstrate that programmed cell death 1 (PD-1) expression in unmanipulated mice identifies a subset of DN T cells with expression of activation-associated markers and a phenotype that strongly suggests they are derived from self-reactive CD8(+) cells. We also found that, within DN T cells, the PD-1(+) subset generates the majority of pro-inflammatory cytokines. Finally, using a TCR-activation reporter mouse (Nur77-GFP), we confirmed that in the steady-state PD-1(+) DN T cells engage endogenous antigens in healthy mice. In conclusion, we provide evidence that indicates that the PD-1(+) fraction of DN T cells represents self-reactive cells.
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