B7 expression on thymic medullary epithelium correlates with epithelium-mediated deletion of V beta 5+ thymocytes.
Recent evidence suggests that I-E+ thymic epithelium, especially medullary epithelium, can induce partial deletion of superantigen-reactive T cells expressing TcR V beta 5, V beta 11, and V beta 17. To seek further information on this issue, we constructed bone marrow chimeras in which MHC class II I-E is expressed on thymic epithelial cells at various levels and locations; the chimeras were reconstituted with stem cells from TcR V beta 5 transgenic mice. Intrathymic deletion of V beta 5 T cells was restricted to relatively mature T cells (expressing high TcR levels), and the degree of deletion correlated with the density of I-E expression in the thymic medulla rather than in the thymic cortex; selective I-E expression in medullary epithelium caused prominent deletion. Interestingly, immunostaining of normal and chimeric mice revealed that expression of B7 (the ligand for CD28) is largely restricted to a subset of medullary epithelial cells; these cells are I-E+ and co-express a specific carbohydrate bound by the lectin UEA-1. B7 expression was lower in thymuses of class II-deficient mice (A beta b-/-) and T-cell-deficient mice (SCID), suggesting that B7 expression is up-regulated during CD4+ thymocyte selection. In support of this idea, B7 expression in the thymus was restored to a normal level in bone marrow reconstituted SCID mice. Because B7 expression correlates with a costimulatory signal for T cells, selective expression of B7 and related antigens on I-E+ medullary epithelium may explain why these cells play a more prominent role in V beta deletion than cortical epithelium.
Degermann
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S
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Surh
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Glimcher
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Sprent
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D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D037102:Lectins / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D037121:Plant Lectins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000276:immunology*
D018122:B7-1 Antigen; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D037102:Lectins; D037121:Plant Lectins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C036850:Ulex europaeus lectins