title: CD4(+) T cells and gamma interferon in the long-term control of persistent friend retrovirus infection.
abstract: We have used the Friend virus model to determine the basic mechanisms by which the immune system can control persistent retroviral infections. Previously we showed that CD4(+) T cells play an essential role in keeping persistent retrovirus in check. The present in vitro experiments with a Friend virus-specific CD4(+) T-cell clone revealed that these cells produce gamma interferon (IFN-gamma), which acts with two distinct mechanisms of antiviral activity. First, IFN-gamma had a direct inhibitory effect on virus production. This inhibitory effect was noncytolytic and, interestingly, was not associated with decreased cell surface expression of viral antigens. The second mechanism of IFN-gamma-mediated antiviral activity was an enhancement of CD4(+) T-cell-mediated cytolytic activity. We also found an in vivo role for IFN-gamma in the control of persistent Friend virus infections. Neutralization of IFN-gamma in persistently infected mice resulted in significantly increased levels of virus in the spleen, and a significant percentage of IFN-gamma-deficient mice were unable to maintain long-term control over Friend virus infections.
authors: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
authors: M
authors: M
authors: Iwashiro
authors: K
authors: K
authors: Peterson
authors: R J
authors: RJ
authors: Messer
authors: I M
authors: IM
authors: Stromnes
authors: K J
authors: KJ
authors: Hasenkrug
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D003602:Cytotoxicity, Immunologic; D005260:Female; D005622:Friend murine leukemia virus; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012192:Retroviridae Infections / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000276:immunology*
chemical_list: D007371:Interferon-gamma