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CD5 levels reveal distinct basal T‐cell receptor signals in T cells from non‐obese diabetic mice
Author(s) -
Dong Mengqi,
Audiger Cindy,
Adegoke Adeolu,
Lebel MarieÈve,
Valbon Stefanie F,
Anderson Colin C,
Melichar Heather J,
Lesage Sylvie
Publication year - 2021
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12443
Subject(s) - t cell receptor , nod , nod mice , biology , cd8 , t cell , cd5 , central tolerance , immunology , microbiology and biotechnology , endocrinology , medicine , antigen , immune system , diabetes mellitus
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.