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

SUMMARY 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 (FlS‐2) is a low oneogenic 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, interferongamma (IFN‐γ) and tumour necrosis factor‐alpha (TNF‐α) were reduced. The suppressed antisheep 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.