Immunobiology of infection with recombinant vaccinia virus encoding murine IL-2. Mechanisms of rapid viral clearance in immunocompetent mice.
CD8+ cytotoxic T (Tc) lymphocytes mediate recovery from vaccinia virus (VV) infection. In mice, anti-VV Tc cells are detectable on or after day 3 after infection, and cytolytic activity peaks between days 5 and 6. A rVV encoding murine IL-2, VV-hemagglutinin (HA)-IL-2, was cleared more rapidly, compared with a control rVV, VV-HA-thymidine kinase (TK), from tissues of infected euthymic normal mice. The mechanism of VV-HA-IL-2 clearance was operative early in infection and correlated with an elevated NK cell response, before the induction of anti-VV Tc cell response. We have investigated the roles of NK cells, T cells, and IFN-gamma in the rapid clearance of VV-HA-IL-2, by using specific mAb. Depletion of NK cells with mAb significantly enhanced VV-HA-IL-2 but not VV-HA-TK titers 3 days after infection. NK cells alone could not account for rapid viral clearance, because VV-HA-IL-2 titers in NK cell-depleted mice were not comparable to VV-HA-TK titers. Treatment with a mAb to IFN-gamma completely abrogated the IL-2-induced mechanism(s) of VV-HA-IL-2 clearance, and titers of the IL-2-encoding virus were comparable to control virus titers. In addition, the elimination of CD4+ but not CD8+ T cells resulted in significant increases in VV-HA-IL-2 titers.
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.
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Karupiah
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Woodhams
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RV
Blanden
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Ramshaw
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D005260:Female; D007371:Interferon-gamma / Q000502:physiology; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology*; D007694:Killer Cells, Natural / Q000502:physiology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000502:physiology; D014615:Vaccinia / Q000276:immunology* / Q000382:microbiology; D014616:Vaccinia virus / Q000302:isolation & purification; D014779:Virus Replication
D007376:Interleukin-2; D007371:Interferon-gamma