Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease.
OBJECTIVE
Regulatory CD25+ T cells (T(reg)) are effective in the prevention and down-regulation of inflammatory bowel disease (IBD) in animal models. Functional T(reg) cells are characterized by the expression of the transcription factor FOXP3 and show a CD4+ CD25(high) phenotype in humans. The aim of this study was to determine whether disease activity in IBD correlates with changes in frequency of T(reg) cells and their distribution in the intestinal mucosa.


METHODS
T(reg) cells were analyzed from peripheral blood and from biopsy specimens of IBD patients, inflammatory controls, and healthy volunteers by flow cytometry (CD4+ CD25(high)), immunochemistry (FOXP3), and real-time PCR (FOXP3). Regulatory properties of purified peripheral CD4+ CD25(high) T(reg) cells were determined by their suppressive effect on the proliferation of CD4+ CD25- T cells.


RESULTS
In peripheral blood, CD4+ CD25(high) T cells from IBD patients retain their suppressive activity. CD4+ CD25(high) and FOXP3+ T(reg) 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+ CD25(high) 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+ T(reg) cells varies with IBD activity. Active IBD is not associated with a functional defect but with a contraction of the peripheral blood T reg pool and an only moderate expansion in intestinal lesions. Thus, compensatory mechanisms, numerically, are not successfully achieved in these diseases.
Maul
Jochen
J
Medical Clinic I, Charité-University Medicine Berlin, Germany.
Loddenkemper
Christoph
C
Mundt
Pamela
P
Berg
Erika
E
Giese
Thomas
T
Stallmach
Andreas
A
Zeitz
Martin
M
Duchmann
Rainer
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D007413:Intestinal Mucosa / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis*
D015375:Receptors, Interleukin-2