Indirect T cell allorecognition: a cyclosporin A resistant pathway for T cell help for antibody production to donor MHC antigens

Abstract

LEW (RT1 1) rats were primed for indirect allorecognition of DA (RT1 avl) MHC molecules by immunizing either with synthetic peptides corresponding to the polymorphic regions of the RT1.A avl classical class I MHC molecule, or with the isolated, denatured chains of the RT1.A class I, RT1.Bα class II and RT1.Bβ class II MHC molecules of the DA strain. These primed LEW rats received DA kidney allografts and were treated after grafting with cyclosporin A. Unprimed LEW controls mount a vigorous rejection response to DA kidney allografts and produce a strong antibody response to DA class I MHC antigens. Both the rejection and the antibody responses are virtually completely suppressed by cyclosporin A treatment in these controls. Priming to indirect allorecognition of donor MHC antigens did not diminish the effectiveness of cyclosporinA in suppressing the acute rejection of DA kidney grafts, but cyclosporin A could not suppress the early antibody response to the grafts in the primed rats. This findinf could be of importance in clinical transplantation, where antibody-mediated graft damage might play an important role in both acute vascular rejection and chronic rejection.