J Aisenberg1, E C Ebert, L Mayer. 1. Division of Gastroenterology, Mount Sinai Medical Center, New York, New York.
Abstract
BACKGROUND: Superantigens are a class of potent T-cell mitogens that activate T cells using specific antigen receptor V regions. Superantigens have been implicated in the pathogenesis of several autoimmune diseases, including inflammatory bowel disease. The present study examines the role of superantigens in the human gastrointestinal immune response. METHODS: Human intestinal epithelial cells and T lymphocytes were obtained from surgical specimens and cultured in the presence or absence of exogenous superantigens. Activation of T cells and V region usage were measured by thymidine incorporation and by cell staining using a panel of monoclonal antibodies. RESULTS: Neither epithelial cells from normal nor diseased intestinal mucosa expressed virally encoded, endogenous superantigens. However, 50% of epithelial cell preparations could present exogenous bacterial superantigens to T cells. In the other 50%, a defect in this function was observed, which did not represent production of suppressive factors or absence of accessory cytokines. Mucosal T lymphocytes proliferated in response to superantigens in vitro, expressing increased transferrin receptor, interleukin-2 receptor, and HLA-DR. CONCLUSIONS: A superantigen-driven mucosal immune response may occur in health and in chronic inflammatory states. The intestinal epithelial cell may mediate this response, through presentation of superantigens to mucosal T lymphocytes.
BACKGROUND: Superantigens are a class of potent T-cell mitogens that activate T cells using specific antigen receptor V regions. Superantigens have been implicated in the pathogenesis of several autoimmune diseases, including inflammatory bowel disease. The present study examines the role of superantigens in the human gastrointestinal immune response. METHODS:Human intestinal epithelial cells and T lymphocytes were obtained from surgical specimens and cultured in the presence or absence of exogenous superantigens. Activation of T cells and V region usage were measured by thymidine incorporation and by cell staining using a panel of monoclonal antibodies. RESULTS: Neither epithelial cells from normal nor diseased intestinal mucosa expressed virally encoded, endogenous superantigens. However, 50% of epithelial cell preparations could present exogenous bacterial superantigens to T cells. In the other 50%, a defect in this function was observed, which did not represent production of suppressive factors or absence of accessory cytokines. Mucosal T lymphocytes proliferated in response to superantigens in vitro, expressing increased transferrin receptor, interleukin-2 receptor, and HLA-DR. CONCLUSIONS: A superantigen-driven mucosal immune response may occur in health and in chronic inflammatory states. The intestinal epithelial cell may mediate this response, through presentation of superantigens to mucosal T lymphocytes.