Pro-inflammatory self-reactive T cells are found within murine TCR-[alpha][beta]+CD4-CD8-PD-1+ cells

• Published in: European journal of immunology Vol. 46; no. 6; p. 1383
• Main Authors: Rodriguez-Rodriguez, Noé, Apostolidis, Sokratis A, Fitzgerald, Lauren, Meehan, Bronwyn S, Corbett, Alexandra J, Martin-Villa, José Manuel, McCluskey, James, Tsokos, George C, Crispin, José C
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01.06.2016
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201546056

TCR-[alpha][beta]+ double negative (DN) T cells (CD3+TCR-[alpha][beta]+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.