IL-4 EXPRESSION BY GRAFTS FROM TRANSGENIC MICE FAILS TO PREVENT ALLOGRAFT-REJECTION

Cell-mediated tissue destruction,such as that occurring in allograft r ejection, is thought to be mediated by Th1 cells and cytokines. We hav e recently shown that transgenic expression of the Th2 cytokine IL-4 b y pancreatic beta cells completely protects nonobese diabetic (NOD) mi ce from autoimmune diabetes by inducing functional tolerance among aut oreactive T cells. To investigate whether local IL-4 production could also induce functional tolerance among alloreactive T cells and thus p revent allograft rejection, we transplanted pancreata from transgenic neonatal mice and their nontransgenic littermates into allogeneic host s. Within 2 wk, recipient mice had rejected their grafts regardless of the transgene's presence or absence, Considering that the vigorous im mune response induced might have prevented any effect by IL-4, we inje cted recipient mice with anti-CD4 and anti-CD8 mAbs, thereby depleting them of T cells and thus providing the islets with an opportunity to mature and grow. This approach indeed delayed rejection of neonatal pa ncreata from nontransgenic mice by >1 wk, By that time, however, pancr eata from transgenic mice had also been rejected, Our results indicate that the allograft rejection response under these conditions, in cont rast to the autoimmune response in NOD mice, cannot be regulated by lo cal IL-4 production, regardless of the cytokine's impact on Th1 cells.