INDUCTION OF T-HELPER-2 IMMUNITY TO AN IMMUNODOMINANT ALLOPEPTIDE

Neonatal tolerance to alloantigens and autoantigens in mice is mediate d by T helper (Th)2 immunity. If a strong and pure Th2 response could be engaged to alloantigens in adult mice, it might result in allograft tolerance. In an attempt to induce Th2 immunity in adults, we studied the T-cell response to peptide I-A beta(k)58-71 (I-Ap), a dominant in direct pathway determinant during rejection of B10.A skin by BALB/c mi ce. Our data show that the naturally occurring response to this peptid e during rejection is Th1, consistent with the notion that Th1 immunit y is central to destruction of the allograft. In contrast, vigorous an d unipolar Th2-type immunity to this peptide can be readily induced by intraperitoneal immunization with incomplete Freund's adjuvant, a pro tocol previously thought to induce T-cell unresponsiveness. Thus, adju vant can be used to Th2-guide the indirect pathway alloresponse in an effort to antagonize naturally occurring Th1 alloimmunity.