Involvement of 4-1BB (CD137)-4-1BBligand interaction in the modulation of CD4 T cell-mediated inflammatory colitis.
4-1BB ligand (4-1BBL) expressed on antigen-presenting cells interacts with 4-1BB on activated T cells (especially CD8+ cells) and co-stimulates the latter to secrete cytokines and to proliferate. The role of 4-1BB-4-1BBL interaction was studied here in a model of colitis based on naive CD4+ T cell transfer to SCID mice, a disease model in which CD8 cells do not take part. We found that CD4+ T cells from 4-1BB-deficient mice, after transfer in SCID mice, proliferated more rapidly compared to wild-type CD4+ T cells. Mice reconstituted with naive CD4+ T cells from 4-1BB-deficient mice developed colitis, however, with a mixed Th1/Th2 response, in contrast to the Th1-type response in mice reconstituted with wild-type naive CD4+ T cells. Importantly, this altered cytokine response did not temper colitis severity. Although it has been reported previously that 4-1BB co-stimulation may contribute to regulatory T cell functioning, we found that CD4+CD25+ regulatory T cells from 4-1BB-deficient mice were perfectly able to prevent naive CD4+ T cell-induced colitis. In conclusion, our data provide evidence that 4-1BB-4-1BBL interaction modulates the effector CD4+ T cell-driven immune response and cytokine production in experimental colitis without affecting regulatory T cell function.
Maerten
P
P
Laboratory of Experimental Immunology, University Hospital, Katholieke Universiteit Leuven, Belgium.
Kwon
B S
BS
Shen
C
C
De Hertogh
G
G
Cadot
P
P
Bullens
D M A
DM
Overbergh
L
L
Mathieu
C
C
Van Assche
G
G
Geboes
K
K
Rutgeerts
P
P
Ceuppens
J L
JL
D053330:4-1BB Ligand; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003092:Colitis / Q000276:immunology*; D003106:Colon / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology; D007150:Immunohistochemistry / Q000379:methods; D017493:Leukocyte Common Antigens / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008643:Mesentery / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009092:Mucous Membrane / Q000276:immunology; D010529:Peritoneal Cavity / Q000473:pathology; D017475:Receptors, Nerve Growth Factor / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D048069:Tumor Necrosis Factors / Q000276:immunology*
D053330:4-1BB Ligand; D015703:Antigens, CD; D016207:Cytokines; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505715:Tnfrsf9 protein, mouse; C505975:Tnfsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D048069:Tumor Necrosis Factors; D017493:Leukocyte Common Antigens