Functional expression of Fas and Fas ligand on human intestinal intraepithelial lymphocytes.
Intestinal intraepithelial lymphocytes (IEL) constitute the first lymphoid compartment to encounter dietary antigens and intestinal pathogens. IEL are proposed to be involved in the defence against bacterial and viral invasion and to play an important role in mucosal immunity. Fas (CD95/APO-1) is a surface receptor that induces apoptotic cell death upon ligation with Fas ligand (FasL). The aim of this study was to examine the expression and function of Fas and FasL on freshly isolated normal human colonic IEL. The expression and function of Fas and FasL on IEL isolated from 40 normal colonic specimens were examined by flow cytometry, reverse transcriptase-polymerase chain reaction, immunohistochemistry, and DNA-release cytotoxicity assay. Virtually all CD3+ IEL (95.2 +/- 4.3%) expressed Fas and were sensitive to agonistic anti-Fas antibody, whereas only 56.6 +/- 8.4% of peripheral T lymphocytes expressed Fas and were resistant to the antibody. We also detected FasL mRNA and protein (40.1 +/- 4.2%) on IEL, and found that IEL exerted FasL-mediated cytotoxicity against Fas-expressing target cells. These findings suggest that human IEL are activated in situ but are tightly regulated by the constitutive expression of functional Fas and FasL to maintain homeostasis of the mucosal immune system.
Morimoto
Y
Y
First Department of Surgery, Okayama University Medical School, Japan.
Hizuta
A
A
Ding
E X
EX
Ishii
T
T
Hongo
T
T
Fujiwara
T
T
Iwagaki
H
H
Tanaka
N
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000302:isolation & purification; D003106:Colon / Q000166:cytology / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000601:surgery; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology; D019014:fas Receptor / Q000302:isolation & purification* / Q000378:metabolism
D017252:CD3 Complex; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor