Treatment of mice with polyinosinic-polycytidilic polyribonucleotide reduces T-cell involvement in a localized inflammatory response to vaccinia virus challenge.
Mice inoculated intracerebrally with 10(3) PFU of vaccinia virus developed a nonfatal meningitis which was maximal 7 days after challenge. Intravenous administration of an interferon (IFN) inducer, polyinosinic-polycytidilic polyribonucleotide [poly(I)-poly(C)], on days 4 and 6 postinjection was associated with a three- to fourfold decrease in the number of T lymphocytes present in cerebrospinal fluid, reflected primarily by a decreased number of vaccinia virus-specific cytotoxic T-lymphocyte precursors. The lack of a concomitant reduction in the overall cytotoxic activity of cerebrospinal fluid cells directed against virus-infected target cells seemed to be largely due to an increase in natural killer cell activity. IFN was implicated as mediating the effect of poly(I)-poly(C) because high systemic levels of IFN were evident after injection, and neither the magnitude of the inflammatory response nor the T-cell levels were affected when poly(I)-poly(C)-treated mice were also given anti-IFN antiserum. However, the poly(I)-poly(C)-induced IFN did not seem to reduce the localized inflammatory response by affecting viral replication in brain tissue because the vaccinia virus titers present on days 6 through 8 of infection were similar to the titers in phosphate-buffered saline controls. These findings are consistent with either an effect of IFN on T-cell recruitment to the central nervous system or an inhibition of proliferation of cells participating in the response. These findings suggest that there is a potential source of complications for clinical protocols that use IFN or inducers to enhance T-cell function in various disease situations, and this effect of IFN may be a contributing factor to the immunosuppression often associated with many viral infections.
Korngold
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R
Doherty
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PC
D000818:Animals; D001921:Brain / Q000382:microbiology; D002555:Cerebrospinal Fluid / Q000166:cytology; D003602:Cytotoxicity, Immunologic; D007372:Interferons / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology; D008587:Meningitis, Viral / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014615:Vaccinia / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000382:microbiology; D014616:Vaccinia virus / Q000254:growth & development
D007372:Interferons; D011070:Poly I-C