Prevention of Diabetes in BB Rats: I. Evidence Suggesting a Requirement for Mature T Cells in Bone Marrow Inoculum of Neonatally Injected Rats

Injection of major histocompatibility complex (MHC)-compatible bone marrow cells from normal animals into neonatal BB rats resulted in a striking decrease in incidence of diabetes and restoration of concanavalin A (ConA) and mixed lymphocyte responses. However, injection of bone marrow cells pretreated with antirat thymocyte antiserum plus complement to remove mature T cells had no effect on incidence of disease, suggesting that mature T cells in the bone marrow inoculum were responsible for prevention of diabetes. Because the decreased incidence of diabetes in rats injected with untreated bone marrow appeared to be unrelated to the extent of lymphopenia in these animals, the involvement of T cells in the onset of diabetes must reflect a defect in the normal function of these cells rather than their absolute number. Approximately 50% of the W3/13⁺ cells in the spleens of BB rats lacked the OX-8 and W3/25 T cell subset markers. The identity of this W3/13⁺, OX-8⁻, W3/25⁻ blank subset remains to be established. Our results, interpreted in light of studies from the other laboratories, suggest the existence of multiple abnormalities in the BB rat, including 1) the presence of T cells as effector or helper cells that augment onset of disease and 2) the absence of a regulatory T cell circuit that could prevent the disease.