An immunosuppressive murine leukaemia virus induces a Th1-->Th2 switch and abrogates the IgM antibody response to sheep erythrocytes by suppressing the production of IL-2.
Many retroviruses have tropism for cells in the immune system and have a propensity to induce immunosuppression in the host. Some of the effects of retroviruses on immune cell function are thought to be mediated through cytokines. Friend ImmunoSuppressive virus-2 (FIS-2) is a low oncogenic murine leukaemia virus (MuLV) that induces lymphadenopathy and immunosuppression in NMRI mice. The role of T cell cytokines during the generation of a primary antibody response in healthy and FIS-2-infected mice was studied following the antibody response to sheep erythrocytes by an in vitro immunization (IVI) technique. In cultures from FIS-2-infected mice, the antibody response was reduced compared with cultures from uninfected mice and the production of the Th2 cytokines IL-4 and IL-6 was elevated, whereas the Th1 cytokines IL-2, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were reduced. The suppressed anti-sheep erythrocyte antibody response in cultures from mice infected with FIS-2 seemed to be caused by an insufficient production of IL-2, since addition of recombinant IL-2 stimulated the antibody response. This effect was also observed in cultures depleted of T cells, indicating a direct effect of IL-2 on B cells. A switch to a Th2 cell response and suppression of IL-2 production might play a central role in the immune cell dysfunction induced by FIS-2.
Institute of Cancer Research, University of Trondheim, Medisinsk Teknisk Centre, Norway.
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Faxvaag
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Espevik
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Dalen
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance; D007075:Immunoglobulin M / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology; D009052:Leukemia Virus, Murine / Q000276:immunology*; D051379:Mice; D012756:Sheep; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007075:Immunoglobulin M; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha