Abstracts of scientific papers - Platform and poster presentations - 2002 AALAS National Meeting - San Antonio, Texas

摘要

Intestinal microbiota and host immunity are integrally linked in large bowel disease and health. Recent studies show that the adaptive immune arm is particularly important in protecting against primary tumor development of intestinal epithelia, but the functions of lymphocytes in this location have not been characterized. To better understand the relationships between intestinal bacteria, immune cells and carcinoma, 129/SvEv Rag2-deficient and 129/SvEv wild type mice were orally inoculated with a widespread enteric mouse bacteria, Helicobacter hepaticus (n = 80), or sham-dosed with media only (n = 30). Inflammatory, hyperplastic, and neoplastic bowel lesions were quantified on a scale of 0-4 with ascending severity, and then compared using Mann-Whitney U nonparametric test for categorical data. Helicobacter-infected Rag2-/-, but not sham-dosed Rag2-/- mice, rapidly developed colitis (P = 0.0001) and large bowel carcinoma (P = 0.0001), demonstrating a link between microbially-driven inflammation and cancer iii the lower bowel. Helicobacter-infected wild type mice did not develop inflammation or carcinoma, indicating that adaptive immunity was required to prevent microbially-induced cancer at this site. Adoptive transfer with CD4+, CD4+ CD25+, or more highly purified CD4+CD25+CD45RBlo regulatory T cells prior to infection with H. hepaticus significantly suppressed inflammation (P < 0.00001) and prevented development of cancer (P < 0.00001). These results suggested that CD4+ regulatory T cells protected against cancer in the intestinal epithelia primarily by preventing bacterially induced innate immune dysregulation at this site. These findings propose a novel role for T cells in protection against colon carcinoma and have implications for new modes of prevention and treatment of cancer in humans.