Gastroenterology

Gastroenterology

Volume 128, Issue 7, June 2005, Pages 1868-1878
Gastroenterology

Clinical-alimentary tract
Peripheral and Intestinal Regulatory CD4+CD25high T Cells in Inflammatory Bowel Disease

https://doi.org/10.1053/j.gastro.2005.03.043Get rights and content

Background & Aims: Regulatory CD25+ T cells (Treg) are effective in the prevention and down-regulation of inflammatory bowel disease (IBD) in animal models. Functional Treg cells are characterized by the expression of the transcription factor FOXP3 and show a CD4+CD25high phenotype in humans. The aim of this study was to determine whether disease activity in IBD correlates with changes in frequency of Treg cells and their distribution in the intestinal mucosa. Methods: Treg cells were analyzed from peripheral blood and from biopsy specimens of IBD patients, inflammatory controls, and healthy volunteers by flow cytometry (CD4+CD25high), immunochemistry (FOXP3), and real-time PCR (FOXP3). Regulatory properties of purified peripheral CD4+CD25high Treg cells were determined by their suppressive effect on the proliferation of CD4+CD25− T cells. Results: In peripheral blood, CD4+CD25high T cells from IBD patients retain their suppressive activity. CD4+CD25high and FOXP3+ Treg cells are increased during remission but decreased during active disease. This contrasts with their strong increase in peripheral blood of patients with acute diverticulitis. Different than peripheral blood, inflamed IBD mucosa contains an increased number of CD4+CD25high T cells, FOXP3+ T cells, and transcripts for FOXP3 compared with noninflamed mucosa. However, the increase of FOXP3+ T cells in IBD lesions is significantly lower compared with inflammatory controls. Conclusions: The frequency of CD4+CD25+ Treg cells varies with IBD activity. Active IBD is not associated with a functional defect but with a contraction of the peripheral blood Treg pool and an only moderate expansion in intestinal lesions. Thus, compensatory mechanisms, numerically, are not successfully achieved in these diseases.

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Subjects

Peripheral blood from 46 patients with CD (24 patients with active and 22 patients with inactive disease; 22 women, 24 men; mean age, 42 years; range, 18–74 years), 28 patients with UC (14 patients with active and 14 patients with inactive disease; 13 women, 15 men; mean age, 41 years; range, 25–89 years), 11 patients with acute diverticulitis (7 women, 4 men; mean age, 59 years; range, 45–73 years), and 16 healthy volunteers (9 women, 7 men; mean age, 31 years; range, 23–57 years) were

Peripheral Blood Treg Are Increased in Inactive and Decreased in Active IBD

Similar to published data,14, 18, 22 we found that CD4+CD25high Treg cells are present in peripheral blood lymphocytes of healthy individuals at a mean of 1.64% (range, 0.6%–3.17%). On flow cytometry, these human Treg cells appear as a subpopulation to the right from the major population of CD4+CD25− and CD4+CD25low cells (Figure 1A).

To determine whether changes in frequency of CD25high Treg cells are present in IBD and correlate with disease activity, we analyzed CD25high surface expression in

Discussion

CD4+CD25+ Treg cells have potent antiinflammatory capacity in animal models of intestinal inflammation.29 To the best of our knowledge, this is the first study that specifically compares the frequency of CD4+CD25+ Treg cells in active vs inactive IBD.

On the mucosal level, we find that the frequency of CD4+CD25+ Treg cells determined by the number of CD4+CD25high T cells, FOXP3+ T cells, and FOXP3 transcripts are consistently increased in active IBD lesions compared with noninflamed areas.

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    Supported by Deutsche Forschungsgemeinschaft grant A2SFB633 (to R.D.) and Z1SFB633 (to M.Z.) and by a grant from the German Federal Department for Research and Education “Kompetenznetz chronisch entzündliche Darmerkrankungen.”

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