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


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.
Hvas
Christian L
CL
Gastro-Immuno Research Laboratory (GIRL), Department of Hepatology and Gastroenterology V, Aarhus University Hospital, Denmark. chvas@as.aaa.dk
Kelsen
Jens
J
Agnholt
Jørgen
J
Höllsberg
Per
P
Tvede
Michael
M
Møller
Jens K
JK
Dahlerup
Jens F
JF
D000328:Adult; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D003092:Colitis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D003113:Colonoscopy; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005470:Fluorometry; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D007778:Lactobacillus; D008297:Male; D008875:Middle Aged; D019936:Probiotics / Q000627:therapeutic use*
D016753:Interleukin-10; D007371:Interferon-gamma