T-cell activation in patients with irritable bowel syndrome.
OBJECTIVE
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 beta7/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-1beta, which also weakly correlated with increased bowel habit dissatisfaction. Furthermore, despite normal frequencies of CD25high T cells in the blood of IBS patients, lower blood CD25high 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.
Department of Internal Medicine, Institute of Medicine, The Sahlgren's Academy, University of Gothenburg, Gothenburg, Sweden. lena.ohman@microbio.gu.se
Lena
L
Ohman
Stefan
S
Isaksson
Ann-Charlotte
AC
Lindmark
Iris
I
Posserud
P-O
PO
Stotzer
Hans
H
Strid
Henrik
H
Sjövall
Magnus
M
Simrén
D000328:Adult; D001707:Biopsy, Needle; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D043183:Irritable Bowel Syndrome / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011336:Probability; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D055815:Young Adult
D016207:Cytokines; D053583:Interleukin-1beta