Staphylococcal enterotoxin B stimulates expansion of autoreactive T cells that induce apoptosis in intestinal epithelial cells: Regulation of autoreactive responses by IL-10

T cell responses to self Ags and normal microbial flora are carefully regulated to prevent autoreactivity, Because IL-10-deficient mice develop colitis, and this response is triggered by luminal flora, we investigated whether IL-10 regulates the ability of microbial Ags to induce autoreactive T cells that could contribute to intestinal inflammation, T cells from mild-type mice were primed with staphylococcal enterotoxin B (SEB) in vitro, which induced an autoreactive proliferative response to syngeneic feeder cells, The cells mere predominately CD3(+) and CD4(+), T cells from IL-10-deficient mice were constitutively autoreactive, and SEE priming enhanced this further, The autoreactive, proliferative response of T cells from wild-type mice was Suppressed by IL-10 in the primary or secondary culture, and this effect was inhibited by neutralizing Abs to the IL-10R. To confirm that an autoreactive repertoire was expanded after SEE priming, we used CBA/J mice (Mls-1(a)) in which autoreactive T cells recognizing the endogenous viral superantigen are depleted (V beta 6, 7, 8.1 TCR-bearing cells). However, SEE rescued these autoreactive T cell repertoires, Adding anti-MHC class II. Ab blocked the autoreactive response. SEE-primed splenic or colonic T cells also induced apoptosis in syngeneic intestinal epithelial cells that was blocked significantly by IL-10. Thus, microbial Ags have the potential to abrogate self tolerance by stimulating autoreactive T cells that become cytolytic to target cells, IL-10 plays a protective role in maintaining self tolerance after microbial stimulation by preventing the activation of T cells that contribute to epithelial cell damage.