PERSISTENT PRODUCTION OF TH2-TYPE CYTOKINES AND POLYCLONAL B-CELL ACTIVATION AFTER CHRONIC ADMINISTRATION OF STAPHYLOCOCCAL-ENTEROTOXIN-B IN MICE

In order to study the immunopathological consequences of repeated expo sure to bacterial superantigens, we evaluated the production of cytoki nes, the profile of serum immunoglobulins and the tissue damage in BAL B/c mice injected twice a week for 3 weeks with 50 mu g of staphylococ cal enterotoxin B (SEB). First, we found that neither interleukin 2 (I L-2) nor interferon gamma (IFN-gamma) were detectable in serum after t he 6th injection of SEB whereas both cytokines were released in the ci rculation 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 injec ted for 3 weeks with SEB produced much lower levels of IL-2 and IFN-ga mma than spleen cells from control mice in response to SEB in vitro wh ereas 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-tr eated mice when rechallenged in vitro with SEB in presence of human ac cessory cells. This TH2-type cytokine profile was associated with a ma rked hyperimmunoglobulinemia and the appearance of anti-mouse immunogl obulin autoantibodies. By Light microscopy, no tissue lesions were obs erved in mice chronically injected with SEB but mesangial deposits of IgG were found in their kidneys by immunofluorescence. We conclude tha t T cell anergy induced by repeated injections of SEB in BALB/c mice i s associated with a persistent production of TH2-type cytokines and a polyclonal B cell activation. (C) 1996 Academic Press Limited