IDENTIFICATION OF MURINE T-CELLS REACTIVE WITH THE BACTERIAL SUPERANTIGEN YERSINIA PSEUDOTUBERCULOSIS-DERIVED MITOGEN (YPM) AND FACTORS INVOLVED IN YPM-INDUCED TOXICITY IN MICE

We previously reported that Yersinia pseudotuberculosis-derived mitoge n (YPM) acts as a superantigen to human T cells. In this study, we ass essed the superantigenicity and toxicity of YPM using murine experimen tal models. YPM activated T cells to produce interleukin-2 in a major histocompatibility complex class II molecule-dependent manner, The T-c ell blasts induced by YPM expressed T-cell receptor (TCR) beta-chain v ariable region (V beta)7, V beta 8.1, V beta 8.2 and V beta 8.3. The i njection of YPM into mice pre-sensitized with D-galactosamine induced lethal shock. This shock was blocked by the injection of monoclonal an tibodies (mAbs) to CD4, TCR V beta 7 plus V beta 8, tumor necrosis fac tor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), but not by inj ection to CD8 or unrelated V beta. These results indicate that YPM-ind uced shock requires the presence of CD4(+) T cells bearing TCR V beta 7 and V beta 8, and that endogenous TNF-alpha and IFN-gamma mediate th e lethal effects.