Regulation of Virally Induced Autoimmunity and Immunopathology: Contribution of LCMV Transgenic Models to Understanding Autoimmune Insulin-Dependent Diabetes Mellitus

Abstract

Viral infections have the capacity to damage host organisms in multiple ways. First, direct lytic effects of the virus can destroy cells or whole organ systems. Second, as discussed in this chapter, the anti-viral immune response can be harmful, in contrast and addition to its beneficial effect of eliminating or decreasing the viral load. For example, cytokines and chemokines secreted by cells and other components of the immune system can have detrimental side effects on particularly sensitive cell types and organs. Via this mechanism, viral infections are excellent candidates for causing chronic self-destructive processes that we think of as autoimmune. A third possibility is that viral infection directly activates antigen-presenting cells (APCs) or inflammatory mediators, ultimately enhancing uptake and presentation of foreign as well as self-antigens and, in this way, producing “true” autoimmunity. It is evident from these considerations that the fine-tuned regulation of anti-viral immunity is crucial and that viral elimination, although it is, of course, the final and most desirable goal, should not be achieved at any cost or through too strong and too rapid an immune response which can damage the host. However, too weak and protracted an anti-viral response may lead to persistent infection with chronic activation of the immune system, which would be harmful in the long-term. In this chapter, I will discuss experimental scenarios illustrating the foregoing considerations. For these studies, we have used the arenavirus, lymphocytic choriomeningitis virus (LCMV) and a transgenic mouse model of virally (LCMV)-induced autoimmune diabetes.