Journal
AMERICAN JOURNAL OF GASTROENTEROLOGY
Volume 104, Issue 5, Pages 1205-1212Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ajg.2009.116
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Funding
- Swedish Medical Research Council [13409]
- Sahlgrenska Academy (LUA/ALF)
- Swedish Society of Medicine
- Magnus Bergvall Foundation
- O. E. and Edla Johansson's Foundation
- Sigurd and Elsa Golje Foundation
- Ollie and Elof Ericsson Foundation
- Sahlgrenska University Hospital Foundation
- Royal Science and Literature Society of Gothenburg
- Tore Nilsson Foundation
- Wilhelm & Martina Lundgren Foundation
- Arla Foods
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OBJECTIVES: Irritable bowel syndrome (IBS) has been found to be associated with low-grade immune activation in a subset of patients. We therefore investigated blood and colonic T-cell activity in IBS patients. METHODS: Blood samples were initially obtained from 74 IBS patients and 30 controls. Supplementary blood samples, to confirm data, were taken from another cohort (26 patients and 14 controls). In addition, colonic biopsies were taken from a third cohort (11 patients and 10 controls). Peripheral blood and colonic mononuclear cells were stimulated with anti-CD3/CD28 antibodies. Proliferation, cytokine secretion, and T-cell phenotype were investigated. IBS symptom severity was assessed. RESULTS: IBS patients displayed an activated phenotype with increased frequencies of blood T cells expressing CD69 and integrin beta 7/HLA-DR. Anti-CD3/CD28-stimulated blood and colonic T cells from IBS patients proliferated less than T cells from controls. IBS patients had an increased polyclonally stimulated T-cell secretion of IL-1 beta, which also weakly correlated with increased bowel habit dissatisfaction. Furthermore, despite normal frequencies of CD25(high) T cells in the blood of IBS patients, lower blood CD25(high) T-cell frequencies were modestly correlated with more bowel habit dissatisfaction and increased total IBS symptom severity. CONCLUSIONS: IBS patients have an increased frequency of activated T cells, demonstrated by the expression of activation markers and reduced proliferation in response to restimulation in vitro. The increased level of T-cell activation is consistent with the hypothesis of low-grade immune activation in IBS and may also be involved in symptom generation in IBS.
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