Contribution of TIA-1+ and granzyme B+ cytotoxic T lymphocytes to cryptal apoptosis and ulceration in active inflammatory bowel disease.
In spite of the clinicopathological differences between Crohn's disease (CD) and ulcerative colitis (UC), they share the fundamental feature of destructive inflammatory processes involving the intestinal wall. The aim of the present study was to investigate the contribution of cell-mediated cytotoxicity to mucosal damage in CD and UC. Colonic mucosal biopsy specimens from patients with active CD (n=25) and UC (n=26) and normal controls (n=12) were immunohistochemically analyzed for the expression of CD3, CD4, CD8, and T cell-restricted intracellular antigen (TIA)-1, which promotes apoptosis by alternative splicing of pre-messenger RNA of the Fas receptor, and granzyme B (GrB), which leads to apoptosis through induction of perforin. Histological scores for cryptal apoptosis and ulceration were assessed in hematoxylin- and eosin-stained sections. In patients with CD and UC, CD3+(P<0.001), CD4+(P<0.001), CD8+(P<0.01), TIA-1+(CD, P<0.01; UC, P<0.001), and GrB+(CD, P<0.01; UC, P<0.001) intraepithelial lymphocytes (IELs) were significantly increased as compared with controls. Positive relationships were found between the histological scores for apoptosis or ulceration and the numbers of CD8+or TIA-1+IELs. In conclusion, cytotoxic T lymphocytes are present in increased numbers in the mucosa of patients with active CD and UC, and local activation of IELs may contribute to mucosal damage with these diseases.
Mitomi
Hiroyuki
H
Department of Clinical Research Laboratory (Pathology Division) National Hospital Organization Sagamihara Hospital, 18-1 Sakura-dai, Sagamihara, Kanagawa 228-8522, Japan. h-mitomi@sagamihara-hosp.gr.jp
Ohkura
Yasuo
Y
Yokoyama
Kaoru
K
Sada
Miwa
M
Kobayashi
Kiyonori
K
Tanabe
Satoshi
S
Fukui
Naoshi
N
Kanazawa
Hideki
H
Kishimoto
Ichiro
I
Saigenji
Katsunori
K
D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000473:pathology; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000737:chemistry / Q000473:pathology*; D003424:Crohn Disease / Q000378:metabolism / Q000473:pathology*; D005260:Female; D053804:Granzymes / Q000032:analysis*; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry / Q000473:pathology; D008297:Male; D008875:Middle Aged; D039102:Poly(A)-Binding Proteins / Q000032:analysis*; D012720:Severity of Illness Index; D000074019:T-Cell Intracellular Antigen-1; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry* / Q000201:enzymology / Q000276:immunology / Q000473:pathology
D017252:CD3 Complex; D039102:Poly(A)-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C509213:GZMB protein, human; D053804:Granzymes