Involvement of 4-1BB (CD137)−4-1BBligand interaction in the modulation of CD4+ T cell-mediated inflammatory colitis
Open Access
- 20 December 2005
- journal article
- Published by Oxford University Press (OUP) in Clinical and Experimental Immunology
- Vol. 143 (2), 228-236
- https://doi.org/10.1111/j.1365-2249.2005.02991.x
Abstract
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.Keywords
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