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Phenotypic and immunoregulatory analysis of intestinal T‐cells in patients with inflammatory bowel disease: evaluation of an in vitro model

Abstract. 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‐γ supplementation of T‐cells derived from uninflamed mucosa significantly (P < 0.001) reduced the CD4+ subset. Treatment with IFN‐γ 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.