ANTIGEN-PRESENTING CELLS IN ADOPTIVELY TRANSFERRED AND SPONTANEOUS AUTOIMMUNE DIABETES

Histological techniques were used to identify antigen-presenting cells (APC) in adoptively transferred diabetes in NOD mice and Ins-HA trans genic mice, and in spontaneously diabetic NOD mice. In adoptively tran sferred disease, CD4+ T cells and F4/80+ macrophages dominated early i nfiltrates. By contrast, in spontaneously developing diabetes in NOD m ice, lymphocytic infiltrates appeared to be well organized around a ne twork of VCAM-1+ NLDC-145+ ICAM-1+ dendritic cells. Thus, the primary APC spontaneous autoimmune disease appears to be the strongly stimulat ory dendritic cell rather than the normally resident macrophage. Next, we used chimeric animals to demonstrate that insulitis and diabetes c ould occur even when responding T cells were unable to recognize islet -specific antigen directly on beta cells. Altogether, the results demo nstrate that immune-mediated damage does not require direct contact be tween CD4+ T cells and beta cells. Moreover, despite the induction of ICAM-1, VCAM-1, and class II on vascular endothelium near islet infilt rates, these experiments show that recruitment of lymphocytes occurs e ven when antigen presentation is not possible on vascular endothelium.