INCREASED APOPTOSIS OF IMMUNOREACTIVE HOST CELLS AND AUGMENTED DONOR LEUKOCYTE CHIMERISM, NOT SUSTAINED INHIBITION OF B7 MOLECULE EXPRESSION ARE ASSOCIATED WITH PROLONGED CARDIAC ALLOGRAFT SURVIVAL IN MICE PRECONDITIONED WITH IMMATURE DONOR DENDRITIC CELLS PLUS ANTI-CD40L mAb1,2

Abstract

The donor-specific acceptance of rejection-prone heart allografts by recipients pretreated with immature donor DC and anti-CD40L mAb is not dependent on sustained inhibition of donor DC CM (CD86) expression. Instead, the pretreatment facilitates a tolerogenic cascade similar to that in spontaneously tolerant liver recipients that involves: (1) chimerism-driven immune activation, succeeded by deletion of host immune responder cells by apoptosis in the spleen and allograft that is linked to interleukin-2 deficiency in both locations and (2) persistence of comparatively large numbers of donor-derived leukocytes. These tolerogenic mechanisms are thought to be generic, explaining the tolerance induced by allografts spontaneously, or with the aid of various kinds of immunosuppression.