ADOPTIVE TRANSFER OF AUTOIMMUNE DIABETES-MELLITUS TO ATHYMIC RATS - SYNERGY OF CD4(-CELLS AND PREVENTION BY RT6(+) T-CELLS() AND CD8(+) T)

We describe the induction and prevention of autoimmune insulin depende nt diabetes mellitus (IDDM), and its pathological substrate, insulitis , in congenitally athymic nude rats following injections of major hist ocompatibility complex (MHC) compatible lymph node T cells. The cells capable of adoptive transfer of autoimmunity were obtained from diabet es resistant (DR) BB rats that had been rendered hyperglycemic by in v ivo depletion of the RT6(+) regulatory T cell subset. We first establi shed that our adoptive transfer assay system is cell dose- and time de pendent and therefore amenable to quantitative analysis. It was also o bserved that both CD4(+) and CD8(+) T cells are required for efficient transfer of autoimmunity. The data indicate that, as in the NOD mouse , a synergistic interaction between CD4(+) and CD8(+) T cells is impor tant for beta cell destruction. Finally, we demonstrated that the admi xture of equal numbers of lymph node T cells, 60% of which were RT6(+) , from intact, non-diabetic DR rats prevented the adoptive transfer of IDDM mediated by diabetogenic T cells from RT6-depleted DR-PR rats. W e conclude that an equilibrium between autoreactive and regulatory cel ls determines the expression of autoimmunity in the DR-BB rat and in t he adoptive transfer of diabetes in quantitative analytical systems.