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

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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-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.