Alloantigen-reactive XXXX development in IL-12-deficient @entity19 .

@entity12782 @entity19 @entity60 @entity1520 @entity715 @entity630 @entity10357
IL-12p70, a 70- to 75-kDa heterodimer consisting of @entity1520 -bonded 35-kDa ( @entity10357 ) and 40-kDa ( @entity12782 ) subunits, enhances @entity630 development primarily by its ability to induce @entity60 production by NK and @entity630 cells. Although homodimers of the @entity12782 subunit of IL-12 are potent IL-12 receptor antagonists in some systems, we have reported that @entity12782 homodimer may accentuate alloreactive CD8+ @entity630 function. To test the role of endogenously produced @entity12782 in alloimmunity, @entity630 development was assessed in either @entity10357 knockout ( @entity10357 -/-) @entity19 , the cells of which are capable of secreting @entity12782 , or @entity12782 knockout ( @entity12782 -/-) @entity19 . Compared with IL-12 wild-type controls, splenocytes obtained from both @entity10357 -/- and @entity12782 -/- @entity19 produced markedly less @entity60 after in vitro stimulation with Con A or alloantigens. Interestingly, in vivo-sensitized @entity630 were detected in both @entity10357 -/- and @entity12782 -/- cardiac allograft recipients. However, in vivo @entity630 development was enhanced in @entity10357 -/- recipients compared with @entity12782 -/- animals, suggesting that endogenous @entity12782 produced in @entity10357 -/- @entity19 may stimulate alloreactive @entity630 . Indeed, neutralizing endogenous @entity12782 with anti- @entity12782 mAb reduced @entity630 development in @entity10357 -/- allograft recipients to that seen in @entity12782 -/- @entity19 . To determine whether @entity630 development that occurred in the absence of IL-12p70 and @entity12782 required @entity60 , @entity12782 -/- allograft recipients were treated with anti- @entity60 mAb. Neutralizing @entity60 did not inhibit in vivo @entity630 development in @entity12782 -/- recipients and resulted in a unique pathology of rejection characterized by vascular @entity715 . Collectively, these data suggest that 1) endogenous @entity12782 may substitute for IL-12p70 in alloantigen-specific @entity630 sensitization in vivo and 2) in vivo alloreactive @entity630 development may occur independent of IL-12 and @entity60 , suggesting an alternate @entity630 -sensitizing pathway.
