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Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2577-81. Epub 2001 Feb 20.

Requirement for natural killer T (NKT) cells in the induction of allograft tolerance.

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  • 1Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba Science City, Ibaraki 305-8575, Japan. seinok@md.tsukuba.ac.jp

Abstract

In this study, we investigated the role of Valpha14 natural killer T (NKT) cells in transplant immunity. The ability to reject allografts was not significantly different between wild-type (WT) and Valpha14 NKT cell-deficient mice. However, in models in which tolerance was induced against cardiac allografts by blockade of lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 or CD28/B7 interactions, long-term acceptance of the grafts was observed only in WT but not Valpha14 NKT cell-deficient mice. Adoptive transfer with Valpha14 NKT cells restored long-term acceptance of allografts in Valpha14 NKT cell-deficient mice. The critical role of Valpha14 NKT cells to mediate immunosuppression was also observed in vitro in mixed lymphocyte cultures in which lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 or CD28/B7 interactions were blocked. Experiments using IL-4- or IFN-gamma-deficient mice suggested a critical contribution of IFN-gamma to the Valpha14 NKT cell-mediated allograft acceptance in vivo. These results indicate a critical contribution of Valpha14 NKT cells to the induction of allograft tolerance and provide a useful model to investigate the regulatory role of Valpha14 NKT cells in various immune responses.

PMID:
11226281
[PubMed - indexed for MEDLINE]
PMCID:
PMC30180
Free PMC Article
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