Positive selection of CD4+ T cells mediated by MHC class II-bearing stromal cell in the thymic cortex.
T lymphocytes differentiate in the thymus, where functionally immature, CD4+CD8+ (double positive) thymocytes develop into functionally mature CD4+ helper cells and CD8+ cytotoxic (single positive) T cells. The thymus is the site where self-reactive T cells are negatively selected (clonally deleted) and where T cells with the capacity to recognize foreign antigens in association with self-proteins encoded by the major histocompatibility complex (MHC) are positively selected. The net result of these developmental pathways is a T-cell repertoire that is both self-tolerant and self-restricted. One unresolved issue is the identity of the thymic stromal cells that mediate the negative and positive selection of the T-cell repertoire. Previous work has pointed to a bone-marrow-derived macrophage or dendritic cell as the inducer of tolerance, whereas a radiation-resistant, deoxyguanosine-resistant thymic cell seems to mediate the positive selection of self-MHC restricted T cells. Thymic stromal cells in the cortex interact with the T-cell antigen receptor on thymocytes. Using several strains of transgenic mice that express the class II MHC molecule I-E in specific regions of the thymus, we show directly that the positive selection of T cells is mediated by an I-E-bearing cell in the thymic cortex.
Bill
J
J
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80262.
Palmer
E
E
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology; D008285:Major Histocompatibility Complex; D051379:Mice; D013950:Thymus Gland / Q000166:cytology*
D000949:Histocompatibility Antigens Class II