Evidence for involvement of clonal anergy in MHC class I and class II disparate skin allograft tolerance after the termination of intrathymic clonal deletion

Y. Tomita, Y. Nishimura, N. Harada, M. Eto, K. Ayukawa, Y. Yoshikai, K. Nomoto

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68 Citations (Scopus)

Abstract

Mechanisms of cyclophosphamide (CP)-induced tolerance to class I (D) and class II (IE) alloantigens were studied. Transplantation tolerance across H-2D plus IE Ag-barriers has been achieved when B10.Thy-1.1 (Kb,IAb,IE-,Db; Thy-1.1) mice were primed i.v. with 9 x 107 spleen cells plus 3 x 107 bone marrow cells from B10.A(5R) mice (5R; kb,IAb,IEb,D(d); Thy-1.2) and treated i.p. with 200 mg/kg of CP 2 days later. The tolerant state in the early and the late stage was confirmed by prolonged acceptance of donor-type skin grafts, and in vitro unresponsiveness to donor Ag. In the tolerant B10.Thy-1.1 mice treated with 5R cells 28 days earlier and followed by CP, intrathymic clonal deletion of Vβ11+ T cells reactive to IE-encoded antigens was observed in association with intrathymic mixed chimerism. 5R skin survived, however, even after the clonal deletion of Vβ11+ T cells terminated by 180 days after tolerance induction. Vβ11+ T cells which reappeared in the periphery of the recipient B10.Thy-1.1 mice bearing 5R skin at this stage, were not capable of proliferating in response to receptor cross-linking with Vβ11-specific mAb. Furthermore, the CTL activity against class I (D(d)) alloantigens of spleen cells from these tolerant mice was restored by the addition of IL-2 to MLC. Thus, our experiments provide direct evidence that tolerance to both class I (D(d)) and class II (IEb) alloantigens by clonal allergy occurs during the termination of intrathymic clonal deletion. These results clearly show practical hierarchy of the mechanisms of transplantation tolerance.

Original languageEnglish
Pages (from-to)4026-4036
Number of pages11
JournalJournal of Immunology
Volume145
Issue number12
Publication statusPublished - Dec 1 1990

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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