ABSENCE OF TNFRP55 INFLUENCES VIRUS-INDUCED AUTOIMMUNITY DESPITE EFFICIENT LYMPHOCYTIC INFILTRATION

Tumor necrosis factor (TNF)-alpha is a multipotent cytokine associated with many cellular functions, including inflammation and anti-viral d efense. Many studies have implicated TNF-alpha in the pathogenesis of autoimmune diseases. TNF-alpha responses are mediated through binding to specific cell surface receptors, TNFRp55 and TNFRp75. The objective of the present study was to investigate the contribution of the TNFRp 55 in the inflammatory response associated with autoimmune diabetes de velopment in a viral transgenic model. In this model, the animals expr ess lymphocytic choriomeningitis virus (LCMV)-glycoprotein (gp) in the beta cells of the pancreas under the control of the rat insulin promo ter (RIP-gp), Diabetes is induced following LCMV infection due to beta cell destruction by LCMV-specific CD8(+) cytotoxic T lymphocytes, TNF Rp55-deficient RIP-gp animals were examined to assess the importance o f the TNFRp55, The kinetics and onset of lymphocytic infiltration into the pancreatic islets and hyperglycemia was not altered in the absenc e of TNFRp55 after LCMV infection. Animals were evaluated following re combinant LCMV-gp vaccinia virus infection to test whether properties of the infectious agent influence autoimmunity. Interestingly, the kin etics were accelerated and the frequency of diabetes was increased in TNFRp55-deficient mice compared with control animals. This accelerated onset of diabetes is likely a result of increased viral replication i n the TNFRp55-deficient host. Thus, these data demonstrate that TNFRp5 5 is not essential for producing the local inflammatory effects which contribute to organ-specific autoimmunity in this transgenic model. Ho wever, the absence of TNFRp55 altered the kinetics and incidence of th e disease in a pathogen-dependent fashion.