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. 1992 Apr 1;89(7):2526–2530. doi: 10.1073/pnas.89.7.2526

Tolerance induction by thymic medullary epithelium.

M W Hoffmann 1, J Allison 1, J F Miller 1
PMCID: PMC48694  PMID: 1557355

Abstract

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.

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Selected References

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