Virus-induced stimulation of T cell responses will be examined in mice infected with either of several viruses, including lymphocytic choriomeningitis, murine cytomegalo, vaccinia, Pichinde, and influenza viruses. Virus-induced stimulation of allospecific cytotoxic T cells (CTL) in C57BL/6 mice will be examined in regard to target specificity, genetic requirements for induction, relationship with other CTL, and regulation by soluble factors. The T cell receptors of virus-specific CTL, virus-induced allospecific CTL, and conventionally induced allospecific CTL will be compared. Similarly, in a second model of polyclonal CTL induction by viruses, the activation of virus specific memory CTL by infections with antigenically distinct viruses will be examined. In certain sequences of virus infection a disease results which neither virus alone would normally induce. This is associated with mononuclear cell infiltration and necrosis of visceral fat. The cellular responses associated with this necrosis will be identified and correlated to the property of the acute virus infections to polyclonally activate CTL. In man, virus infections have been associated with allograft rejections, tumor remissions, and development of autoimmunity. Studying the mechanism of virus-induced polyclonal CTL stimulation may help in the understanding of these potent pathological sequelae of virus infections.
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