High‐Dose Survival in the Lymphocytic Choriomeningitis Virus Infection Is Accompanied by Suppressed DTH but Unaffected T‐Cell Cytotoxicity

Abstract

Provided that intracerebral inoculation is applied, an increase in the virus dose from 102 to 104 LD50 of lymphocytic choriomeningitis virus (LCMV) leads to strikingly reduced mortality. To analyze the background for this autointerference, several virologic and immunologic variables were measured in mice infected with these doses of virus. In the high-dose mice, generally higher organ virus titers and serum interferon titers were found than in the low-dose mice. Since virus-specific T-cell cytotoxicity in spleen, peripheral blood and meningeal exudate was similar after intracerebral infection with large and small virus doses, and since the LCMV infection in the brain qualitatively and quantitatively was independent of the size of virus inoculum, the explanation for the survival of the high-dose animals is obviously not lack of possibilities for interaction between cytotoxic T cells and infected sensitive targets in the CNS. High doses of virus caused a clear suppression of the LCMV-specific delayed-type hypersensitivity (DTH). When splenocytes from high-dose animals were transferred either i.v. or locally into the footpad of newly virus-challenged mice, DTH was markedly suppressed as compared with the response after transfer of spleen cells from low-dose mice. Autointerference in the LCMV infection evidently is due to a selective suppression of Td [T cell mediating DTH] function. Large amounts of persistent virus late after infection with high doses of virus suggest a central role for Td function also in virus clearance. The existence of 2 subsets of K.D region-restricted T cells, one mediating cytotoxicity and the other mediating DTH, is indicated.