The expression profile of functional regulatory T cells, CD4+CD25high+/forkhead box protein P3+, in patients with ulcerative colitis during active and quiescent disease.
Regulatory T cells (T(reg)) have an essential role in maintaining immune tolerance in the gut. The functional CD4(+) T(reg) express the transcription factor forkhead box protein 3 (FoxP3) or a CD25(high) in humans. Further, depletion of elevated granulocytes/monocytes by extracorporeal adsorption (GMA) induces immunomodulation in patients with ulcerative colitis (UC). We investigated the impact of GMA on T(reg). Thirty-one UC patients, clinical activity index (CAI) 12.1 +/- 2.97, refractory to conventional medications including intravenous corticosteroid and 13 healthy controls (HC), were included. Patients received five GMA sessions over 5 weeks. Biopsies from the rectal mucosa and blood samples at baseline and post-GMA were immunostained with anti-CD4/FoxP3 and anti-CD4/CD25 antibodies for immunohistochemistry and flow cytometry. Following GMA, 22 of 31 patients achieved remission (CAI <or= 4, P < 0.01) and their endoscopic activity index decreased from 10.6 +/- 2.32 to 4.75 +/- 1.48 (P = 0.003). The circulating CD4(+)CD25(high+) T(reg) level was low and increased markedly in responders (P < 0.02). In the nine non-responders, the baseline CD4(+)CD25(high+) T(reg) level was about 50% of the level in the responders (P < 0.03) or in the HC (P < 0.01), and all nine had to undergo colectomy. Conversely, the number of CD4(+)/FoxP3(+) mucosal T(reg) in GMA responders decreased significantly after the fifth GMA session compared with the baseline level (P < 0.05). It is believed that the CD4(+) T(reg) has an essential role in the control of immune pathology in UC patients and a net influx of these cells from the circulation into the mucosa may proceed to suppress inflammation. GMA can impact the circulating as well as the mucosal levels of T(reg).
Kamikozuru
K
K
Department of Lower Gastroenterology, Hyogo College of Medicine, Hyogo, Japan.
Fukunaga
K
K
Hirota
S
S
Hida
N
N
Ohda
Y
Y
Yoshida
K
K
Yokoyama
Y
Y
Tozawa
K
K
Kawa
K
K
Iimuro
M
M
Nagase
K
K
Saniabadi
A R
AR
Nakamura
S
S
Miwa
H
H
Matsumoto
T
T
D000327:Adsorption; D000328:Adult; D015704:CD4 Antigens / Q000032:analysis*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis*; D005938:Glucocorticoids / Q000627:therapeutic use; D006098:Granulocytes / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis*; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D005938:Glucocorticoids; D053645:Interleukin-2 Receptor alpha Subunit