PMID: 9637486Jun 24, 1998Paper

Thymus requirement and antigen dependency in the "infectious" tolerance pathway in transplant recipients

The Journal of Immunology : Official Journal of the American Association of Immunologists
K OnoderaJ W Kupiec-Weglinski

Abstract

We have shown that features of infectious tolerance, as originally described in thymectomized mice, may be applied to euthymic rat recipients of heart transplants. We now report on studies aimed at exposing mechanisms underlying the infectious tolerance pathway, with emphasis on the role of thymus and alloantigen. Pretransplant thymectomy diminished the efficacy of CD4-targeted therapy, with donor-specific tolerance induced in approximately 50% of recipients. Thymus was required for generation of regulatory T cells under the cover of CD4 mAb therapy and for the ability of these cells to confer infectious tolerance. However, thymus was not mandatory to maintain an infectious-permissive environment in cohorts of adoptively transferred recipients. Intragraft expression of IL-2, IL-4, and IL-10 genes was diminished in euthymic and thymectomized tolerant hosts. However, grafts in the latter group showed significant IFN-gamma gene expression, suggesting a less efficient down-regulation of Th1-like cells in the absence of regulatory cells. Indeed, exogenous challenge with rIL-2 or freshly alloactivated spleen cells recreated rejection in thymectomized, but not euthymic, hosts, suggesting that a state of cytokine-responsive anergy cont...Continue Reading

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