CD8+ T cells in a normal host limit autoimmune attack by CD-8+ effector T cells (P4541)

Abstract

Abstract We have developed a mouse model of diabetes by adoptively transferring small numbers of OT1 cells into animals expressing OVA under the rat insulin promoter (RIP-OVA). These cells are activated in vivo with a Picornavirus (TMEV) expressing OVA antigen. Titrating the dose of adoptively transferred cells, changes disease outcome. Mice receiving low amounts of cells develop hyperglycemia, and recover homeostasis. Investigation of recovered animals revealed normal blood glucose regulation. Pancreatic histology of recovered mice showed extensive pancreatic destruction with no or very few remaining insulin-positive islets. While adoptively transferred OT1 cells were present, pancreas infiltrating T cells were largely endogenous. To evaluate the functional importance of the host T cells, we tested disease progression using RAG KO, CD4 KO, and CD8 KO RIP-OVA hosts. Without RAG, CD4, or CD8 we observed increased disease severity. This change is not attributed to homeostatic proliferation in the CD4 and CD8 KO animals, as adoptively transferred OT1 cells behaved similarly in the KO hosts in comparison to RIP-OVA mice. However there is significant homeostatic proliferation occurring in the RIP-OVA RAG KO animals. Our studies reveal the importance of CD4 and CD8 T cells in limiting autoimmune attack in the pancreas. Although populations of CD4 T regulatory cells are well known, the importance of CD8 T cells in limiting inflammation are less well characterized.