TY - JOUR
T1 - High-dose survival in the lymphocytic choriomeningitis virus infection is accompanied by suppressed DTH but unaffected T-cell cytotoxicity
AU - Marker, O
AU - Thomsen, Allan Randrup
AU - Volkert, M
AU - Hansen, B L
AU - Clemmensen, I H
N1 - Keywords: Animals; Antibodies, Viral; Antigens, Viral; Brain; Female; Hypersensitivity, Delayed; Interferons; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Male; Mice; Mice, Inbred C3H; Spleen; T-Lymphocytes, Cytotoxic; Virus Replication
PY - 1985
Y1 - 1985
N2 - Provided that intracerebral inoculation is applied, an increase in the virus dose from 10(2) to 10(4) LD50 of lymphocytic choriomeningitis virus (LCMV) leads to strikingly reduced mortality. To analyse the background for this autointerference, we measured several virologic and immunologic variables in mice infected with these doses of virus. In the high-dose mice we found generally higher organ virus titres and serum interferon titres than in the low-dose mice. Since we could demonstrate that 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 central nervous system. On the other hand, high doses of virus caused a clear suppression of the LCMV-specific delayed-type hypersensitivity (DTH). In addition, when splenocytes from high-dose animals were transferred either intravenously 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. We therefore conclude that autointerference in the LCMV infection is due to a selective suppression of Td 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. Finally, our results indicate the existence of two subsets of K,D region-restricted T cells, one mediating cytotoxicity and the other mediating DTH. This possibility is discussed.
AB - Provided that intracerebral inoculation is applied, an increase in the virus dose from 10(2) to 10(4) LD50 of lymphocytic choriomeningitis virus (LCMV) leads to strikingly reduced mortality. To analyse the background for this autointerference, we measured several virologic and immunologic variables in mice infected with these doses of virus. In the high-dose mice we found generally higher organ virus titres and serum interferon titres than in the low-dose mice. Since we could demonstrate that 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 central nervous system. On the other hand, high doses of virus caused a clear suppression of the LCMV-specific delayed-type hypersensitivity (DTH). In addition, when splenocytes from high-dose animals were transferred either intravenously 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. We therefore conclude that autointerference in the LCMV infection is due to a selective suppression of Td 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. Finally, our results indicate the existence of two subsets of K,D region-restricted T cells, one mediating cytotoxicity and the other mediating DTH. This possibility is discussed.
M3 - Journal article
C2 - 2578691
SN - 0301-6323
VL - 21
SP - 81
EP - 91
JO - Scandinavian Journal of Immunology, Supplement
JF - Scandinavian Journal of Immunology, Supplement
IS - 1
ER -