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Empirical studies attempting to explain tolerance to transplanted tissues have demonstrated a regulatory role for CD4+ T-cells. We here propose that regulatory T-cells mediating transplantion tolerance comprise two sets which can functionally complement each other. The CD4+CD25+ "natural regulator" arises in the thymus, and is preoccupied with self-antigens expressed at sites of inflammation. The second, comprising both CD4+CD25+ (FoxP3+) and CD4+CD25- Tr1-like cells are induced by persistent danger-free antigen in the periphery. The role of these cells is to moderate immune responses to prevent tissue destruction while allowing microbial elimination.

Original publication




Journal article


Semin Immunol

Publication Date





119 - 126


Animals, Antigens, CD, CD4-Positive T-Lymphocytes, DNA-Binding Proteins, Forkhead Transcription Factors, Humans, Immune Tolerance, Models, Immunological, Organ Transplantation, Receptors, Interleukin-2, Self Tolerance, T-Cell Antigen Receptor Specificity, T-Lymphocyte Subsets, T-Lymphocytes, Thymus Gland, Transplantation Immunology