Apoptosis resistance in ulcerative colitis: high expression of decoy receptors by lamina propria T cells.
Intestinal mucosa is constantly exposed to normal environmental antigens. A significant number of intestinal mucosal T cells are being deleted through apoptosis. In contrast, T cells from inflamed mucosa of ulcerative colitis patients did not undergo apoptosis. In this study, we determined whether the apoptosis of normal mucosal T cells was induced by antigen receptor stimulation and further determined pathways that mediated the apoptosis. Freshly isolated lamina propria T cells were stimulated with CD3 mAb and apoptosis was determined by Annexin V staining. Normal mucosal T cells underwent apoptosis upon CD3 mAb stimulation whereas the T cells from inflamed mucosa did not. The apoptosis in normal T cells was blocked by TRAIL-R1:Fc and an inhibiting CD95 antibody. Interestingly, decoy receptor (DcR)1, DcR2, and DcR3 that compete with death receptor (DR)4/5 and CD95 were highly expressed by the T cells from inflamed mucosa, but much lower by T cells from normal mucosa. Our data suggest that normal mucosal T cells are constantly deleted in response to environmental antigens mediated through DR4/5 and CD95 pathways and mucosal T cells from ulcerative colitis resist to undergoing apoptosis due to highly expression of DcR1, DcR2, and DcR3.
Fayad
Raja
R
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago Medical Center, Maywood, IL 60153, USA.
Brand
Marc I
MI
Stone
David
D
Keshavarzian
Ali
A
Qiao
Liang
L
D000328:Adult; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology*; D053222:Fas Ligand Protein; D005260:Female; D058851:GPI-Linked Proteins; D006262:Health; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism*; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand; D053319:Tumor Necrosis Factor Decoy Receptors; D000079424:Tumor Necrosis Factor Inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053221:TNF-Related Apoptosis-Inducing Ligand; C108661:TNFRSF10C protein, human; C505653:TNFSF10 protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D000079424:Tumor Necrosis Factor Inhibitors; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors