Direct CD1d-Mediated Stimulation of APC IL-12 Production and Protective Immune Response to Virus Infection In Vivo

摘要: CD1d-restricted NKT cells rapidly stimulate innate and adaptive immunity through production of Th1 and/or Th2 cytokines induction CD1d(+) APC maturation. However, therapeutic exploitation has been hampered by their paucity defects in human disease. cell-APC interactions can be modeled direct stimulation APCs CD1d vitro. We have now found that ligation with multiple mAbs also stimulated bioactive IL-12 release from but not knockout murine splenocytes Moreover, all the tested induced as well both IFN-gamma IFN-alpha vivo CD1d-deficient recipients. Unlike IFN-gamma, CD1d-induced was at least partially dependent on invariant cells. Optimal resistance to infection picornavirus encephalomyocarditis virus is known require CD1d-dependent IL-12-induced IFN-alpha. enhanced systemic IL-12, protective against virus, suggesting an alternative interpretation for previous results involving "blocking" other systems. Such responses, including elevations cytokines, were seen F(ab')(2)s vivo, whereas IgM mAb (with presumably minimal tissue penetration) comparably effective protection cytokine Although acting immediately "downstream," later during than cell agonist alpha-galactosylceramide. These data indicate bypassed CD1d-mediated robust immunity, which may potential directly adjuvant.