Critical roles for IL-4, IL-5, and eosinophils in chronic skin allograft rejection

C57BL/6 mice injected with the 145-2C11 anti-CDS mAb and grafted with MHC c lass II disparate bm12 skin develop a chronic rejection characterized by in terstitial dermal fibrosis, a marked eosinophil infiltrate, and an oblitera tive intimal vasculopathy. Because these changes occur in the absence of al loreactive antibodies, we examined the contribution of cytokines in their p athogenesis. Chronically rejected grafts showed a marked accumulation of bo th IL-4 and IL-5 mRNA. Mixed lymphocyte reaction experiments established th at mice undergoing chronic rejection were primed for IL-4, IL-5, and IL-10 secretion. In vivo administration of anti-IL-4 mAb completely prevented all ograft vasculopathy as well as graft eosinophil infiltration and dermal fib rosis. Injection of anti-IL-5 mAb or the use of IL-5-deficient mice as reci pients also resulted in the lack of eosinophil infiltration or dermal fibro sis, but these mice did develop allograft vasculopathy. Administration of a nti-IL-10 mAb did not influence any histologic parameter of chronic rejecti on. Thus, in this model, IL-4- and IL-5-mediated tissue allograft eosinophi l infiltration is associated with interstitial fibrosis. IL-4, but not eosi nophils, is also required for the development of obliterative graft arterio lopathy.