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

Seino KI, Fukao K, Muramoto K, Yanagisawa K, Takada Y, Kakuta S, Iwakura Y, Van Kaer L, Takeda K, Nakayama T, Taniguchi M, Bashuda H, Yagita H, Okumura K
Proc Natl Acad Sci U S A. 2001 98 (5): 2577-81

PMID: 11226281 · PMCID: PMC30180 · DOI:10.1073/pnas.041608298

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.

MeSH Terms (11)

Adaptation, Physiological Animals CD28 Antigens Graft Rejection Intercellular Adhesion Molecule-1 Killer Cells, Natural Lymphocyte Culture Test, Mixed Lymphocyte Function-Associated Antigen-1 Mice Mice, Inbred BALB C Transplantation, Homologous

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