Direct CD1d-mediated stimulation of APC IL-12 production and protective immune response to virus infection in vivo.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Simon YueMark A Exley

Abstract

CD1d-restricted NKT cells rapidly stimulate innate and adaptive immunity through production of Th1 and/or Th2 cytokines and induction of CD1d(+) APC maturation. However, therapeutic exploitation of NKT cells has been hampered by their paucity and defects in human disease. NKT cell-APC interactions can be modeled by direct stimulation of human APCs through CD1d in vitro. We have now found that direct ligation with multiple CD1d mAbs also stimulated bioactive IL-12 release from CD1d(+) but not CD1d knockout murine splenocytes in vitro. Moreover, all of the CD1d mAbs tested also induced IL-12 as well as both IFN-gamma and IFN-alpha in vivo from CD1d(+) but not CD1d-deficient recipients. Unlike IFN-gamma, CD1d-induced IFN-alpha was at least partially dependent on invariant NKT cells. Optimal resistance to infection with picornavirus encephalomyocarditis virus is known to require CD1d-dependent APC IL-12-induced IFN-gamma as well as IFN-alpha. CD1d ligation in vivo enhanced systemic IL-12, IFN-gamma, and IFN-alpha and was protective against infection by encephalomyocarditis virus, suggesting an alternative interpretation for previous results involving CD1d "blocking" in other systems. Such protective responses, including elevations ...Continue Reading

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Jul 17, 2012·Journal of Leukocyte Biology·Hemangi B ShahMark L Lang
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