TOLERANCE INDUCTION BY THYMIC MEDULLARY EPITHELIUM

To study the role of thymic medullary epithelium in tolerance inductio n, the third and fourth branchial clefts of embryos from E-mu-K(b) tra nsgenic mice, which express the major histocompatibility complex class I antigen H-2K(b) exclusively on medullary thymic epithelium, were gr afted to athymic nude mice. The grafts differentiated into tissue that morphologically resembled normal thymus. These grafts expressed the H -2K(b) antigen appropriately and gave rise to a functional T cell repe rtoire. In vivo tolerance to H-2K(b) disparate skin grafts was invaria bly found in mice expressing H-2K(b) in the medulla or in both medulla and cortex of C57BL/6 branchial cleft-grafted controls. In marked con trast, in vitro cytotoxicity assays demonstrated reactivity toward H-2 K(b) in the presence of interleukin 2, and limiting-dilution analyses showed similar frequencies of cytolytic T cell precursors reactive to H-2K(b) and to third-party stimulators. Medullary epithelium can, ther efore, induce split tolerance, in which in vivo tolerance is accompani ed by strong in vitro responses in the presence of interleukin 2.