Classic virus diseases (smallpox, polio, measles) are being vaccinated out of existance. Attention is now turnning to those virus diseases displaying an immunopathological nature. A model system is described to assess the lethal role of Delayed-type Hypersensitivity (DTH) Thymus-derived (T) lymphocytes in central nervous system (CNS) disease. The murine Lymphocytic Choriomeningitis (LCM) virus system we employ centers around the strains of virus which, after i.c. injection of adult mice, lead to strikingly different outcomes. One virus, termed docile, does not kill but induces life-long infection. The other virus, termed aggressive, kills all mice within 7-9 days. Although virus-specific cytotoxic thymus-derived lymphocytes (CTL) have been considered to be rather intimately involved in the pathogenetic pattern we have found little difference in their numbers in the spleen and meningeal infiltrate (MI) of mice infected with either virus. Furthermore in the absence of any indication that viral tropisms for brain targets might be different, we have turned our attention to recent reports from several laboratories indicating that cells with DTH activity could be central to the disease process. Using MI cells from mice infected with either virus we will assess, by adoptive transfer experiments (injecting cells from a donor mouse into a genetically identical recipient mouse), their ability to cause lethal disease as well as an accelerated foot pad response. If cell populations have these biological activities we will determine if they are restricted in their activity by recognition of the major histocompatability antigens (by adoptive transfer of cells into congenic mice - mice differing from the donor cells by a small number of defined alleles) as well as those defined by Lyt l and Lyt 2 monoclonal antibodies and complement. Since accessory phagocytic cells play a major role in DTH reactions MI cells from mice infected with either type of virus will be exmined (in tissue culture) for macrophage content, activity, and ability to support replication of these LCM viruses, as well as ability to serve as targets for LCM-specific CTLs. Knowledge gained from these studies may be useful in dissecting the control mechanisms involved in DTH genesis.
