Over-expression of interleukin 10 in mucosal T cells of patients with active ulcerative colitis.
Ulcerative colitis (UC), a chronic inflammatory bowel disease, exhibits pronounced increase of T lymphocytes in the inflamed mucosa. To understand the role of intestinal T lymphocytes in the pathogenesis of UC their cytokine production in the mucosa was analysed. Intestinal T lymphocytes of UC, Crohn's disease and control patients were analysed for cytokine mRNA levels by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) directly after isolation without in vitro stimulation. Frequencies of cytokine positive cells were determined in UC and control colon by immunomorphometry. T lymphocytes in normal colon expressed interleukin (IL)-2, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1, but not IL-4, IL-5 or IL-10. In UC, a highly significant increase in IL-10 mRNA levels in T lymphocytes and an increased frequency of IL-10 positive cells was seen in colon. IL-10 mRNA levels were also elevated in T lymphocytes of the non-inflamed ileum and correlated with disease activity at both locations. CD4+ T lymphocytes were the major source of IL-10 mRNA. IL-2, IFN-gamma and TNF-alpha mRNA levels were decreased in colonic T lymphocytes, and virtually no IL-2, IFN-gamma, TNF-alpha or TGF-beta positive cells were detected in basal lymphoid aggregates. However, scattered IL-10 positive cells were found here. Lamina propria outside the aggregates contained IL-10-, IFN-gamma, TNF-alpha and TGF-beta but not IL-2 positive cells. T cells of UC patients did not express IL-4 or IL-5. Taken, together the data suggest a generalized activation of IL-10 producing CD4+ T cells along the intestine of UC patients. The local environment seems to determine the biological consequences of elevated IL-10.
Melgar
S
S
Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
Yeung
M M-W
MM
Bas
A
A
Forsberg
G
G
Suhr
O
O
Oberg
A
A
Hammarstrom
S
S
Danielsson
A
A
Hammarstrom
M-L
ML
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000276:immunology*; D003106:Colon / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D007376:Interleukin-2; D015848:Interleukin-5; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma