Selective decrease in colonic CD56(+) T and CD161(+) T cells in the inflamed mucosa of patients with ulcerative colitis.
OBJECTIVE
To investigate the role of local colonic mucosal NK receptor-positive T (NKR(+) T) cells in the regulation of intestinal inflammation, we analyzed the population and function of these cells in ulcerative colitis (UC).


METHODS
Colonic mucosal tissues were obtained from colonoscopic biopsies of the descending colon from 96 patients with UC (51 endoscopically uninflamed, 45 inflamed) and 18 normal controls. Endoscopic appearance and histologic score at the biopsied site were determined by Matts' classification. A single cell suspension was prepared from each biopsy by collagenase digestion. Two NKR(+) T cell subsets, CD56(+) (CD56(+)CD3(+)) T cells and CD161(+) (CD161(+)CD3(+)) T cells, were detected by flow cytometric analysis. Intracellular cytokine analysis for anti-inflammatory cytokine interleukin-10 (IL-10) was performed by in vitro stimulation with phorbol-myristate-acetate (PMA) and ionomycin.


RESULTS
CD56(+) T cells and CD161(+) T cells are present in the normal human colon and account for 6.7% and 21.3% of all mononuclear cells, respectively. The populations of both CD56(+) T cells and CD161(+) T cells were decreased significantly in the inflamed mucosa of UC. In contrast, the frequency of conventional T cells (CD56(-)CD3(+) cells and CD161(-)CD3(+) cells) was similar among the patient and control groups. The populations of NKR(+) T cells were correlated inversely with the severity of inflammation, which was classified according to the endoscopic and histologic Matts' criteria. Interestingly, approximately 4% of mucosal NKR(+) T cells expressing IL-10 were detected by in vitro stimulation with PMA and ionomycin.


CONCLUSIONS
Selective reduction in the population of colonic mucosal NKR(+) T cells may contribute to the development of intestinal inflammation in UC.
Shimamoto
Masaru
M
Department of Medicine and Molecular Science, Hiroshima University, Hiroshima 734-8551, Japan.
Ueno
Yoshitaka
Y
Tanaka
Shinji
S
Onitake
Toshiko
T
Hanaoka
Rie
R
Yoshioka
Kyoko
K
Hatakeyama
Tsuyoshi
T
Chayama
Kazuaki
K
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000954:Antigens, Surface / Q000378:metabolism*; D001379:Azathioprine / Q000494:pharmacology / Q000627:therapeutic use; D019002:CD56 Antigen / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D016753:Interleukin-10 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D037181:Lectins, C-Type / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000954:Antigens, Surface; D019002:CD56 Antigen; D007166:Immunosuppressive Agents; D007476:Ionophores; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016753:Interleukin-10; D015759:Ionomycin; C016658:phorbolol myristate acetate; D011239:Prednisolone; D001379:Azathioprine; D013755:Tetradecanoylphorbol Acetate