The relationship of blood transfusion and immunosuppression to the Th1/Th2 paradigm

Abstract

A lthough current drug protocols used to prevent organ rejection in transplant recipients have been highly successful, recipients must take anti-rejection drugs for the rest of their lives and endure risk of opportunistic infections and lymphoproliferative disorders. An alternative strategy would be to induce donor-specific tolerance using a short term protocol. We have previously demonstrated that a single donor-specific blood transfusion (DST) combined with a short course of cyclosporine A (CsA) significantly prolongs the survival of cardiac allografts in the high responding AC1 to Lewis rat model.’ The addition of a third agent, such as rapamycin, IL-4 or nutritional therapy to this protocol produces long-term tolerance in a significant number of recipients.2-4 Overly aggressive immunosuppression in this model does not improve allograft survival and in some cases decreases it.5 The mechanisms responsible for these observations are not completely understood. Recent studies of cytokine profiles associated with allograft rejection and tolerance induction suggest the ThUTh2, Tcl/Tc2 paradigm as a mechanism of tolerance with a Th2 phenotype being associated with tolerance and a Thl phenotype closely linked to rejection.‘j In order to elucidate the possible role played by these cell types and cytokines, we monitored the production of IL-4 and INF-y from CD3+CD4’ and CD3’CD8+ lymphocytes in an AC1 to Lewis rat allograft model.