Functional expression of 4-1BB (CD137) in the inflammatory tissue in Crohn's disease.
4-1BB ligand (L) expressed on antigen presenting cells (APC) interacts with 4-1BB, expressed on activated T cells and this interaction costimulates T cells to secrete cytokines and to proliferate. We investigated whether 4-1BB/4-1BBL interactions might be involved in the pathogenesis of Crohn's disease (CD). In immunohistochemistry, we found 4-1BB expression on lamina propria (LP) cells in inflamed and to a lesser extend in non-inflamed gut tissue from CD patients. mRNA levels for 4-1BB were also elevated in intestinal CD tissue. In contrast, only few 4-1BB-expressing cells were found in inflamed tissue from ulcerative colitis (UC) patients and almost no positive cells were found in control intestinal tissue. 4-1BB expression was better sustained on in vitro activated lamina propria T cells from CD patients compared to controls. Finally, agonistic anti-4-1BB antibody enhanced interferon-gamma (IFN-gamma) production and proliferation of lamina propria T cells from CD patients. Taken together, our data suggest that 4-1BB/4-1BBL interactions contribute to the persistence of gut inflammation in CD.
Clinical Immunology, University Hospital, Katholieke Universiteit Leuven, Leuven, Belgium.
Philippe
P
Maerten
Karel
K
Geboes
Gert
G
De Hertogh
Chong
C
Shen
Pascal
P
Cadot
Dominique M A
DM
Bullens
Gert
G
Van Assche
Freddy
F
Penninckx
Paul
P
Rutgeerts
Jan L
JL
Ceuppens
D053330:4-1BB Ligand; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D002455:Cell Division; D003424:Crohn Disease / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D007700:Kinetics; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053330:4-1BB Ligand; D015703:Antigens, CD; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505714:TNFRSF9 protein, human; C505974:TNFSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma