1 Department of Medical Microbiology and Immunology, Faculty of Health Sciences, Aarhus University, Aarhus University2 Klinisk Mikrobiologisk Afdeling, SKS, Faculty of Health Sciences, Aarhus University, Aarhus University3 The Department of Hepatology and Gastroenterology V, Faculty of Health Sciences, Aarhus University, Aarhus University4 Århus universitetshospital5 Department of Clinical Medicine - The Department of Hepatology and Gastroenterology V, Department of Clinical Medicine, Health, Aarhus University6 Department of Biomedicine - Forskning og uddannelse, Øst, Department of Biomedicine, Health, Aarhus University7 Rigshospitalet8 Department of Clinical Medicine - The Department of Hepatology and Gastroenterology V, Department of Clinical Medicine, Health, Aarhus University9 Department of Biomedicine - Forskning og uddannelse, Øst, Department of Biomedicine, Health, Aarhus University
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.
Scandinavian Journal of Gastroenterology, 2007, Vol 42, Issue 5, p. 592-601