Tolerance induction by thymic medullary epithelium.
To study the role of thymic medullary epithelium in tolerance induction, the third and fourth branchial clefts of embryos from E mu-Kb transgenic mice, which express the major histocompatibility complex class I antigen H-2Kb exclusively on medullary thymic epithelium, were grafted to athymic nude mice. The grafts differentiated into tissue that morphologically resembled normal thymus. These grafts expressed the H-2Kb antigen appropriately and gave rise to a functional T cell repertoire. In vivo tolerance to H-2Kb disparate skin grafts was invariably found in mice expressing H-2Kb in the medulla or in both medulla and cortex of C57BL/6 branchial cleft-grafted controls. In marked contrast, in vitro cytotoxicity assays demonstrated reactivity toward H-2Kb in the presence of interleukin 2, and limiting-dilution analyses showed similar frequencies of cytolytic T cell precursors reactive to H-2Kb and to third-party stimulators. Medullary epithelium can, therefore, induce split tolerance, in which in vivo tolerance is accompanied by strong in vitro responses in the presence of interleukin 2.
Hoffmann
M W
MW
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Allison
J
J
Miller
J F
JF
D000818:Animals; D003602:Cytotoxicity, Immunologic; D004848:Epithelium / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D007108:Immune Tolerance; D007111:Immunity, Cellular; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D008822:Mice, Transgenic; D016038:Skin Transplantation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000033:anatomy & histology / Q000276:immunology*
D006183:H-2 Antigens