T cell specificity and cross reactivity towards enterobacteria, Bacteroides, Bifidobacterium, and antigens from resident intestinal flora in humans

Abstract

Background - T cell responses to normal intestinal bacteria or their products may be important in the immunopathogenesis of chronic enterocolitis. Aims - To investigate the T cell specificity and cross reactivity towards intestinal bacteria. Patients/Methods - T cell clones were isolated with phytohaemagglutinin from peripheral blood and biopsy specimens of inflamed and non-inflamed colon from five patients with inflammatory bowel disease (IBD) and two controls. T cell clones were restimulated with anaerobic Bacteroides and Bifidobacteria species, enterobacteria, and direct isolates of aerobic intestinal flora. T cell phenotype was analysed by single-cell immunocyte assay. Results - Analysis of 96 T cell clones isolated from peripheral blood and biopsy specimens from two patients with IBD showed that both Bifidobacterium and Bacteroides species specifically stimulate proliferation of CD4+TCRαβ+ T cell clones from both sites and that cross reactivity exists between these anaerobic bacteria and different enterobacteria. Analysis of 210 T cell clones isolated from three patients with IBD and two controls showed that indigenous aerobic flora specifically stimulate T cell clones from peripheral blood and biopsy specimens from a foreign subject. Some of these flora specific T cell clones were cross reactive with defined enterobacteria. In addition, T cell clones stimulated by their own indigenous aerobic flora were identified in patients with IBD. Conclusion - Immune responses to antigens from the intestinal microflora involve a complex network of T cell specificities.