Virus-triggered immune suppression in mice caused by virus-specific cytotoxic T cells.
Normal mice infected with 10(5) infectious doses of lymphocytic choriomeningitis virus (LCMV, WE isolate) generated a reduced or no T cell-independent IgM and/or T cell-dependent IgG response to a subsequent vesicular stomatitis virus Indiana (VSV-IND) injection; this transient immune suppression lasted for weeks to months. Connatally infected LCMV-carrier mice or acutely infected T cell-deficient nude mice had normal anti-VSV IgM and IgG or IgM responses respectively. LCMV-infected nude mice transfused with helper cell-depleted LCMV-specific immune spleen cells were immunosuppressed. Normal mice infected with LCMV but treated with a rat anti-CD8 mAb (that had been shown previously to eliminate cytotoxic T cells in vivo) and then infected with VSV exhibited a normal anti-VSV IgM and IgG response. Since no IFN-alpha or -beta was detected on, or after, day 6 of LCMV infection, neither LCMV alone, nor IFN induced by it caused the observed immune suppression; the presented evidence suggests that LCMV-immune CD8+ T cells were responsible for it. It is conceivable that a similar pathogenesis where virus-specific cytotoxic T cells may destroy virus-infected cells essentially involved in an immune response (APC, T helper cells, etc.) may be involved in other virally triggered immune suppression or in AIDS.
Leist
T P
TP
Institut für Pathologie, Universitätsspital, Zürich, Switzerland.
Rüedi
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E
Zinkernagel
R M
RM
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D003588:Cytopathogenic Effect, Viral; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007153:Immunologic Deficiency Syndromes / Q000209:etiology*; D008216:Lymphocytic Choriomeningitis / Q000150:complications / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology; D008811:Mice, Inbred DBA / Q000276:immunology; D008819:Mice, Nude / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M