Fas/Fas ligand expression and characteristics of primed CD45RO+ T cells in the inflamed mucosa of ulcerative colitis.
BACKGROUND
Chronic immune activation in the colon is characteristic of ulcerative colitis (UC). Fas/Fas ligand (FasL) system is a mechanism responsible for activation-induced cell death (AICD), which maintains homeostasis within the immune system. Thus, Fas/FasL expression on activated colonic T cells of UC patients, as well as the susceptibility of such T cells to AICD was investigated in order to determine the role of activated colonic T cells in the long lasting inflammation in UC.


METHODS
Fas, FasL, and CD45RO expression on peripheral blood and colonic T cells of UC patients were assayed by flow cytometry. Apoptosis of colonic T cells induced by anti Fas antibody was assessed using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay.


RESULTS
The majority of colonic T cells expressed both CD45RO and Fas in the colonic mucosa, a situation that was quite different from that in the peripheral blood. The number of CD45RO+CD8+ and Fas+CD8+ T cells was significantly lower in UC patients than the controls, unlike the number of Fas+CD4+ T cells. In contrast, the number of both CD45RO+CD4+ and CD45RO+CD8+ T cells in UC mucosa expressing FasL was significantly higher than in the controls. While Fas mediated apoptosis of CD45RO+CD8+ T cells was higher in UC patients than the controls, the number of apoptotic CD45RO+CD4+ T cells from UC mucosa was not.


CONCLUSIONS
In UC patients, CD45RO+CD4+ T cells are less sensitive to apoptotic signals mediated by Fas. These phenomena may contribute to the pathogenesis of UC.
Suzuki
A
A
Third Dept of Internal Medicine, Niigata University School of Medicine, Japan.
Sugimura
K
K
Ohtsuka
K
K
Hasegawa
K
K
Suzuki
K
K
Ishizuka
K
K
Mochizuki
T
T
Honma
T
T
Narisawa
R
R
Asakura
H
H
D000328:Adult; D017209:Apoptosis; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
D015704:CD4 Antigens; D016827:CD8 Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor; D017493:Leukocyte Common Antigens