Persistent production of TH2-type cytokines and polyclonal B cell activation after chronic administration of...

In order to study the immunopathological consequences of repeated exposure to bacterial superantigens, we evaluated the production of cytokines, the profile of serum immunoglobulins and the tissue damage in BALB/c mice injected twice a week for 3 weeks with 50 micrograms of staphylococcal enterotoxin B (SEB). First, we found that neither interleukin 2 (IL-2) nor interferon gamma (IFN-gamma) were detectable in serum after the 6th injection of SEB whereas both cytokines were released in the circulation after the first injection. In contrast, interleukin 4 (IL-4) and interleukin 10 (IL-10) serum levels were similar after the first and the sixth injection of SEB. Likewise, spleen cells from mice injected for 3 weeks with SEB produced much lower levels of IL-2 and IFN-gamma than spleen cells from control mice in response to SEB in vitro whereas their production of IL-10 was not significantly altered. Both IL-4 and IL-10 were found to be secreted by purified T cells from SEB-treated mice when rechallenged in vitro with SEB in presence of human accessory cells. This TH2-type cytokine profile was associated with a marked hyperimmunoglobulinemia and the appearance of anti-mouse immunoglobulin autoantibodies. By light microscopy, no tissue lesions were observed in mice chronically injected with SEB but mesangial deposits of IgG were found in their kidneys by immunofluorescence. We conclude that T cell anergy induced by repeated injections of SEB in BALB/c mice is associated with a persistent production of TH2-type cytokines and a polyclonal B cell activation.