Adoptively transferable tolerance induced by CD45RB monoclonal antibody

The phenomenon of rejection remains the most serious problem in transplanta tion. The ultimate goal in transplant immunology is to develop therapeutic strategies that lead to tolerance. It has been shown that two injections of a monoclonal antibody to CD45RB leads to indefinite acceptance of renal al lografts in mice. Moreover, the CD45RB monoclonal antibody reverses acute r ejection and still induces tolerance. The purpose of this study was to asse ss mechanisms that could underlie this therapeutic benefit. It was shown th at splenic lymphocytes from tolerant animals augmented proliferation in all ogeneic mixed lymphocyte reactions against donor alloantigens, and the seru m of tolerant mice contained donor-specific antibodies, mainly of the IgG1 isotype, suggesting the presence of TH2 cytokines. Tolerance could not be b roken by interleukin-2 infusion, but tolerance could be adoptively transfer red by transfusion of tolerant mouse CD4(+) splenic lymphocytes into naive allografted animals. These data suggest that an active immunoregulatory mec hanism is partly responsible for the therapeutic effect. CD45RB-directed th erapy may find clinical application in organ transplantation in human patie nts.