Resistance to anti-CD45RB-induced tolerance in NOD mice: mechanisms involved

While great advances have been made in the success of islet transplantation to cure autoimmune diabetes, this protocol remains limited by our inability to induce donor-specific tolerance within the recipient. The profound resistance of the NOD mouse to tolerance-inducing regimens that are routinely successful in other strains further defines the imposing barriers that must be surmounted. Herein, we have assessed the utility of anti-CD45RB therapy to induce tolerance to allografts in C57BL/6 and NOD-strain mice. We find that, as with other therapies, NOD mice are also resistant to this manipulation, despite robust tolerance induction in the comparison strain. Analysis of cell surface markers revealed a number of changes within the B lymphocyte compartment following contact with antibody and alloantigen in the B6 strain. The absence of reciprocal changes within the NOD lymphocyte compartment suggests that B cells might contribute to the mechanism of action of this therapy and to the resistance to immunological tolerance noted in the NOD strain.