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Spatiotemporal regulation of peripheral T cell tolerance

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The incomplete removal of T cells that are reactive against self-proteins during their differentiation in the thymus requires mechanisms of tolerance that prevent their effector function within the periphery. A… Click to show full abstract

The incomplete removal of T cells that are reactive against self-proteins during their differentiation in the thymus requires mechanisms of tolerance that prevent their effector function within the periphery. A further challenge is imposed by the need to establish tolerance to the holobiont self, which comprises a highly complex community of commensal microorganisms. Here, we review recent advances in the investigation of peripheral T cell tolerance, focusing on new insights into mechanisms of tolerance to the gut microbiota, including tolerogenic antigen-presenting cell types and immunomodulatory lymphocytes, and their layered ontogeny that underlies developmental windows for establishing intestinal tolerance. While emphasizing the intestine as a model tissue for studying peripheral T cell tolerance, we highlight overlapping and distinct pathways that underlie tolerance to self-antigens versus commensal antigens within a broader framework for immune tolerance. Description

Keywords: cell; peripheral cell; regulation peripheral; tolerance; spatiotemporal regulation; cell tolerance

Journal Title: Science
Year Published: 2023

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