Phenotypic and immunoregulatory analysis of intestinal T-cells in patients with inflammatory bowel disease: evaluation of an in vitro model.
Although a disturbed immune response to constituents of the gut mucosa has been implicated in the pathogenesis of inflammatory bowel disease, the mechanisms are still unclear. Intestinal T-cells derived from gut biopsies were propagated in vitro as single and co-cultures under different experimental conditions prior to flow cytometry. Intestinal T-cell lines from inflamed mucosa (n = 69) showed a significant (P < 0.001) decrease in CD4+ T-cells compared to T-cells from normal (n = 49) and uninflamed (n = 29) tissue specimens. Co-culturing of inflamed and uninflamed mucosa led to a normalization of CD4+ T-cells in cultures derived from inflamed mucosa. Analysis of supernatants revealed a significantly (P < 0.001) increased secretion of IL-4 under co-culture conditions. Moreover, stimulation of cultures derived from inflamed mucosa with rIL-4 led to a significant (P < 0.001) increase in CD4+ T-cells, whereas anti-IL-4 antibodies or IFN-gamma supplementation of T-cells derived from uninflamed mucosa significantly (P < 0.001) reduced the CD4+ subset. Treatment with IFN-gamma and anti-IL-4 antibodies did not affect the phenotype of T-cells derived from inflamed mucosa. These data suggest that IL-4 might play a key role in the intestinal immune response. Furthermore, this in vitro system allows the investigation of mucosal immune mechanisms in more detail under standardized conditions.
Niessner
M
M
Abteilung Innere Medizin II, Gastroenterologie, Klinikum der Albert-Ludwigs-Universität, Freiburg, Germany.
Volk
B A
BA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000473:pathology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta