Evidence that clonal anergy is induced in thymic migrant cells after anti-cd4-mediated transplantation tolerance

Susan E. Alters, Howard Song, C. Garrison Fathman

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Diabetic (B6) (IE“) mice treated with a depleting regimen of anti-CD4 monoclonal antibody at the time of transplantation with A/J (IEk) islets of Langerhans showed indefinite acceptance of their islet allograft, as evidenced by persistent normoglycemia. To address the mechanisms involved in such anti-CD4 induced transplantation tolerance we studied potentially IE-reactive Vβ11+ T cells from the tolerant allografted mice. Following complete repopulation of the CD4+ cells, both the CD4+Vβ11+ and CD8+11+ T cell subsets of the transplanted mice were unresponsive to anti-Vβ11 specific crosslinking. In contrast, lymphocytes tested within the first ten days following transplant were responsive to anti-Vβ11 specific crosslinking; this response decreased as a function of time and reached background levels by day 120 posttransplant. Sorting experiments indicated that the response of lymphocytes to anti-Vβ11 specific crosslinking seen during the initial 120 days posttransplant was confined to the peripheral CD8+ cells; the repopulating CD4+Vβ11+ T cells were unresponsive. In addition, administration of r-IL-2 at the time of transplantation induced rejection in anti-CD4-treated animals, again indicating that the peripheral CD8+ cells could respond shortly after transplant if provided with appropriate help. The decreasing response of CD8+ T cells from transplanted animals to anti-Vβ11 stimulation was inversely correlated with the rate of migration of cells from the thymus to the periphery, implying that new thymic migrant Vβ11+ cells, both CD4+ and CD8+, were rendered anergic upon encountering peripheral alloantigen. These data suggest the possibility that recent thymic migrants are rendered anergic upon encountering antigen in the periphery, a simple model to serve as a “fail-safe” mechanism to prevent autoreactivity.

Original languageEnglish (US)
Pages (from-to)633-638
Number of pages6
JournalTransplantation
Volume56
Issue number3
StatePublished - 1993
Externally publishedYes

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Clonal Anergy
Transplantation Tolerance
T-Lymphocytes
Lymphocytes
Transplants
Isoantigens
Graft Rejection
T-Lymphocyte Subsets
Islets of Langerhans
Thymus Gland
Cell Movement
Interleukin-2
Allografts
Transplantation
Monoclonal Antibodies
Antigens

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Evidence that clonal anergy is induced in thymic migrant cells after anti-cd4-mediated transplantation tolerance. / Alters, Susan E.; Song, Howard; Fathman, C. Garrison.

In: Transplantation, Vol. 56, No. 3, 1993, p. 633-638.

Research output: Contribution to journalArticle

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