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T Cell Autoreactivity by Design: A Theoretical Framework for Understanding Tolerance, Autoimmunity, and Transplant Rejection

Cleveland Clinic Foundation

Self-reactive T lymphocytes are largely but not entirely eliminated from the host’s T cell repertoire during development through central thymic deletion. Standard immunologic paradigms suggest that the residual autoreactive T cells represent a threat to the host as they have the potential to initiate autoimmune disease. An alternative viewpoint is that the autoreactive T cells are released into the periphery by design and that they participate in the maintenance of self-tolerance through regulatory mechanisms. This theoretical framework is consistent with many of the experimental observations made in tolerant allograft recipients and provides a foundation through which one can make sense of the recently described interrelationship between autoreactive T cells and alloreactive T cells in transplantation immunobiology.

Key Words: allograft rejection • autoimmunity • T lymphocytes • tolerance • regulatory cells

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