Browsing by Author "Brutkiewicz, R. R."

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    Critical role of NKT cells in posttransplant alloantibody production
    (Wiley Blackwell (Blackwell Publishing), 2014-11) Zimmerer, J. M.; Swamy, P.; Sanghavi, P. B.; Wright, C. L.; Abdel-Rasoul, M.; Elzein, S. M.; Brutkiewicz, R. R.; Bumgardner, G. L.; Department of Microbiology & Immunology, IU School of Medicine
    We previously reported that posttransplant alloantibody production in CD8-deficient hosts is IL-4+ CD4+ T cell-dependent and IgG1 isotype-dominant. The current studies investigated the hypothesis that IL-4-producing natural killer T cells (NKT cells) contribute to maximal alloantibody production. To investigate this, alloantibody levels were examined in CD8-deficient WT, CD1d KO and Jα18 KO transplant recipients. We found that the magnitude of IgG1 alloantibody production was critically dependent on the presence of type I NKT cells, which are activated by day 1 posttransplant. Unexpectedly, type I NKT cell contribution to enhanced IgG1 alloantibody levels was interferon-γ-dependent and IL-4-independent. Cognate interactions between type I NKT and B cells alone do not stimulate alloantibody production. Instead, NKT cells appear to enhance maturation of IL-4+ CD4+ T cells. To our knowledge, this is the first report to substantiate a critical role for type I NKT cells in enhancing in vivo antibody production in response to endogenous antigenic stimuli.