CD5 levels reveal distinct basal T‐cell receptor signals in T cells from non‐obese diabetic mice. Issue 6 (8th March 2021)

• Record Type: Journal Article
• Authors: Dong, Mengqi; Audiger, Cindy; Adegoke, Adeolu; Lebel, Marie‐Ève; Valbon, Stefanie F; Anderson, Colin C; Melichar, Heather J; Lesage, Sylvie
• Is Part Of: Immunology and cell biology. Volume 99:Issue 6(2021)
• Page Start: 656
• Page End: 667
• Publication Date: 2021-03-08
• Subjects: B6. H2g7 -- CD5 -- NOD -- TCR signals -- thymic selection; Immunology -- Periodicals; Cytology -- Periodicals; 616.079
• DOI: 10.1111/imcb.12443
• Languages: English
• ISSNs: 0818-9641

Abstract

Abstract: Type 1 diabetes in non‐obese diabetic (NOD) mice occurs when autoreactive T cells eliminate insulin producing pancreatic β cells. While extensively studied in T‐cell receptor (TCR) transgenic mice, the contribution of alterations in thymic selection to the polyclonal T‐cell pool in NOD mice is not yet resolved. The magnitude of signals downstream of TCR engagement with self‐peptide directs the development of a functional T‐cell pool, in part by ensuring tolerance to self. TCR interactions with self‐peptide are also necessary for T‐cell homeostasis in the peripheral lymphoid organs. To identify differences in TCR signal strength that accompany thymic selection and peripheral T‐cell maintenance, we compared CD5 levels, a marker of basal TCR signal strength, on immature and mature T cells from autoimmune diabetes‐prone NOD and ‐resistant B6 mice. The data suggest that there is no preferential selection of NOD thymocytes that perceive stronger TCR signals from self‐peptide engagement. Instead, NOD mice have an MHC‐dependent increase in CD4 + thymocytes and mature T cells that express lower levels of CD5. In contrast, T cell‐intrinsic mechanisms lead to higher levels of CD5 on peripheral CD8 + T cells from NOD relative to B6 mice, suggesting that peripheral CD8 + T cells with higher basal TCR signals may have survival advantages in NOD mice. These differences in the T‐cell pool in NOD mice may contribute to the development or progression of autoimmune diabetes. Abstract : Using CD5 expression as a marker of basal T‐cell receptor (TCR) signal strength, we revisit how NOD polyclonal T cells perceive TCR signals and the impact on the T‐cell pool. In NOD mice, we find preferential selection of CD4 + T cells expressing low levels of CD5 and accumulation of CD8 + T cells expressing high levels of CD5. Both alterations probably contribute to autoimmune susceptibility.