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The blockade of CD28-B7 costimulation pathway after administration of the fusion protein CTLA4Ig prevents acute and chronic allograft (Tx) rejection and may induce tolerance in some animal transplant models. This study was designed to investigate the efficacy of and interactions between CTLA4Ig and donor allo-Ag in a well-defined model of accelerated rejection of cardiac Tx in presensitized rat recipients.
Cd4-targeted therapy with a nondepleting (RIB-52 monoclonal antibody (mAb) abrogates accelerated rejection and produces permanent acceptance of cardiac allografts in presensitized rat recipients, in association with diminished host circulating allo-Ab responses, induction of peripheral allospecific T cell unresponsiveness in vitro and in vivo, and profound depression of both Th1- and Th2-type cytokines...
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