Crohn's disease intestinal CD4+ T cells have impaired interleukin-10 production which is not restored by probiotic bacteria

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OBJECTIVE: Crohn's disease (CD) has been associated with low mucosal interleukin (IL)-10 production, but the mechanism behind this deficiency remains unclear. The aim of this study was to investigate IL-10 and interferon (IFN)-gamma production in intestinal CD4+ T cells from CD patients and healthy volunteers (HV) and to examine how this was affected by bacterial products and the presence or absence of autologous dendritic cells.

MATERIAL AND METHODS: We cultured intestinal CD4+ T cells from CD patients (n=9) and HV (n=6) and differentiated dendritic cells from their peripheral monocytes. Intestinal T cells were stimulated with Lactobacillus strains or autologous intestinal bacteria in the presence or absence of dendritic cells. IL-10 and IFN-gamma were measured on day 4.

RESULTS: When there were autologous dendritic cells present, CD intestinal T cells produced high levels of IFN-gamma (mean 6.4 ng/ml+/-standard error of the mean 1.1 ng/ml) but low levels of IL-10 (0.7 ng/ml+/-0.1 ng/ml). In contrast, HV intestinal T cells produced less IFN-gamma (3.9 ng/ml+/-0.8 ng/ml, p=0.06) and more IL-10 (4.6 ng/ml+/-0.9 ng/ml, p=0.0001) than CD intestinal T cells. Co-culture with Lactobacilli failed to revert this imbalance in CD, but tended to do so in HV. When there were no dendritic cells, CD intestinal T cells responded to autologous bacteria with an increased IFN-gamma production (2.3+/-1.3 ng/ml) compared with HV intestinal T cells (0.3+/-0.2 ng/ml).

CONCLUSIONS: Crohn's disease intestinal CD4+ T cells display a pro-inflammatory cytokine profile with impaired production of the regulatory cytokine IL-10. Tolerogenic bacteria (Lactobacilli) failed to restore this regulatory defect.

Original languageEnglish
Book seriesScandinavian Journal of Gastroenterology. Supplement
Volume42
Issue5
Pages (from-to)592-601
Number of pages10
ISSN0036-5521
DOIs
Publication statusPublished - May 2007

    Research areas

  • Adult, Biopsy, CD4-Positive T-Lymphocytes, Cells, Cultured, Colitis, Colon, Colonoscopy, Crohn Disease, Dendritic Cells, Female, Fluorometry, Follow-Up Studies, Humans, Interferon-gamma, Interleukin-10, Intestinal Mucosa, Lactobacillus, Male, Middle Aged, Probiotics, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't

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