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A wide variety of suppressive pathways have been investigated in efforts to understand the basis for immune tolerance. Although the contribution of CD4+ regulatory T cells (Tregs) to self-tolerance has been extensively studied, less attention has been given to CD8+ Tregs. Here we review recent insights into the development, function, and potential clinical applications of this regulatory subset. We focus on CD8+ Tregs that recognize self-peptides associated with MHC-Ib products and that express Ly49/KIR (killer cell immunoglobulin-like receptor) coinhibitory receptors. Recent analyses of their T cell receptor repertoire, thymic differentiation, and mechanism of suppression are summarized. Identification of the human homolog of these cells has suggested new strategies for CD8+ Treg-dependent immunotherapy for autoimmune disease and cancers.
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Vuttaradhi et al. (2025) studied this question.
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