Total colectomy improves altered distribution of regulatory T cells in patients with ulcerative colitis.
BACKGROUND
It is now generally believed that regulatory T cells (Tregs) play an important role in peripheral tolerance, and a defect in Tregs is considered one of the most important factors in the induction of various kinds of autoimmune disease including ulcerative colitis (UC). Here, we examined the change in frequency of Tregs phenotype in five patients with UC whose condition had not been controllable by conventional conservative therapy and who were scheduled for total colectomy.


OBJECTIVE
The aim of this study was to elucidate the role of Tregs in the pathogenesis of UC in a clinical setting.


METHODS
Peripheral blood mononuclear cells (PBMCs) were obtained from five patients with UC, and the change in frequency of Tregs was analyzed by flow cytometry before total colectomy and on postoperative days 1, 7, and 20. Tregs were defined as CD4+ CD25+ CD45RA+ T cells, and data (%) were expressed as frequency of Tregs/CD4+ T cells. Peripheral blood mononuclear cells (PBMCs) from healthy blood donors (n = 5) and from patients undergoing other types of major surgery (n = 5) were used as controls.


RESULTS
Comparison with normal subjects showed that generation of Tregs was suppressed in UC patients before they underwent total colectomy (0.95 versus 5.06; P = 0.009). The frequency of Tregs increased shortly after total colectomy. The frequency at postoperative days 1, 7, and 20 was 3.81%, 8.13%, and 3.76%, respectively. There were significant differences in the change in frequency in the period before surgery and postoperative day 1, between postoperative days 1 and 7, and between days 7 and 20.


CONCLUSIONS
Elimination of targeted antigens residing in the colorectal mucosa by total colectomy improved the suppressed distribution of Tregs in UC patients. The present study provides the first direct clinical evidence that Tregs play a pivotal role in the pathogenesis of UC.
Department of Second Surgery, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga-gun, Tochigi 321-0293, Japan.
Makoto
M
Furihata
Tokihiko
T
Sawada
Toshie
T
Okada
Mitsuru
M
Ishizuka
Toru
T
Horie
Kazutoshi
K
Takagi
Hitoshi
H
Nagata
Keiichi
K
Kubota
D000328:Adult; D015704:CD4 Antigens / Q000097:blood; D003082:Colectomy; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000601:surgery*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000097:blood; D017634:Self Tolerance / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015704:CD4 Antigens; D015375:Receptors, Interleukin-2; D017493:Leukocyte Common Antigens