EVIDENCE FOR SUPERANTIGEN PRODUCTION BY YERSINIA-PSEUDOTUBERCULOSIS

Yersinia pseudotuberculosis is an enteric pathogen that induces a variety of clinical symptoms, fever, scarlatiniform rash, diarrhea, vomiting, and arthritis. Characteristic histopathologic findings in Y. pseudotuberculosis infection such as lymphoid hyperplasia, typically seen in mesenteric lymph nodes, suggest that the stimulation of a large proportion of T lymphocytes may be involved in the pathogenesis of this infection. In this study, we assessed the mitogenic activity of culture supernatants of the clinical isolates of Y. pseudotuberculosis and investigated the mechanism by which these culture sups activate T cells. The culture sups, as well as partially purified fractions obtained by gel filtration, were found to selectively stimulate T cells bearing Vbeta3, Vbeta9, Vbeta13.1, and Vbeta13.2 compared with stimulation by anti-CD3. Furthermore, fibroblasts transfected with different HLA class II molecules, either HLA-DPw9, -DQw6, -DR1, or -DR4 Dw15, were capable of presenting Y pseudotuberculosis culture supernatants to purified T cells. The T cell response to this sup was not restricted by donor HLA-DR types and was not neutralized by antibodies against the known staphylococcal superantigens, Staphylococcal enterotoxin (SE)A, SEB, SEC2, SED, SEE, and TSST1. These results suggest that Y. pseudotuberculosis produces superantigenic toxins that may mediate some of the systemic illnesses associated with infection by this organism.