Biphasic activity of cd137 ligand-stimulated monocytes on T cell apoptosis and proliferation
CD137L (4-1BBL) is a member of the TNFSF and is expressed on APCs as a transmembrane protein. Reverse signaling by CD137L in monocytes causes cell activation and differentiation to mature inflammatory DCs that can stimulate T cell proliferation. However, CD137L agonists have also been reported to in...
| Main Authors: | , , , , |
|---|---|
| Format: | Journal Article |
| Published: |
Society for Leukocyte Biology
2011
|
| Online Access: | http://hdl.handle.net/20.500.11937/50933 |
| _version_ | 1848758571324407808 |
|---|---|
| author | Shaqireen Kwajah, M. Mustafa, N. Holme, A. Pervaiz, Shazib Schwarz, H. |
| author_facet | Shaqireen Kwajah, M. Mustafa, N. Holme, A. Pervaiz, Shazib Schwarz, H. |
| author_sort | Shaqireen Kwajah, M. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | CD137L (4-1BBL) is a member of the TNFSF and is expressed on APCs as a transmembrane protein. Reverse signaling by CD137L in monocytes causes cell activation and differentiation to mature inflammatory DCs that can stimulate T cell proliferation. However, CD137L agonists have also been reported to induce apoptosis in PBMCs. This study aimed at clarifying these seemingly opposing activities. We find that the dying cells within PBMCs are T cells and that this T cell death is dependent on monocytes and correlates with the monocyte:T cell ratio. This CD137L-induced, monocytemediated T cell apoptosis is reminiscent of MDCD, and both are cell contact-dependent. T cell death is not mediated by CD95 or DR4 or -5 but by ROS produced by the T cells. T cell apoptosis is restricted to the first 24 h of stimulation, and at later time-points, the monocytes differentiate to inflammatory DCs under the influence of CD137L signaling and acquire the capacity to stimulate T cell proliferation from Day 4 onward. This biphasic activity may contribute to infection-induced T cell attrition, where in the early phase (<24 h) of an infection, massive T cell apoptosis occurs before the antigen-specific T cells expand. © Society for Leukocyte Biology. |
| first_indexed | 2025-11-14T09:46:06Z |
| format | Journal Article |
| id | curtin-20.500.11937-50933 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:46:06Z |
| publishDate | 2011 |
| publisher | Society for Leukocyte Biology |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-509332017-09-13T15:34:25Z Biphasic activity of cd137 ligand-stimulated monocytes on T cell apoptosis and proliferation Shaqireen Kwajah, M. Mustafa, N. Holme, A. Pervaiz, Shazib Schwarz, H. CD137L (4-1BBL) is a member of the TNFSF and is expressed on APCs as a transmembrane protein. Reverse signaling by CD137L in monocytes causes cell activation and differentiation to mature inflammatory DCs that can stimulate T cell proliferation. However, CD137L agonists have also been reported to induce apoptosis in PBMCs. This study aimed at clarifying these seemingly opposing activities. We find that the dying cells within PBMCs are T cells and that this T cell death is dependent on monocytes and correlates with the monocyte:T cell ratio. This CD137L-induced, monocytemediated T cell apoptosis is reminiscent of MDCD, and both are cell contact-dependent. T cell death is not mediated by CD95 or DR4 or -5 but by ROS produced by the T cells. T cell apoptosis is restricted to the first 24 h of stimulation, and at later time-points, the monocytes differentiate to inflammatory DCs under the influence of CD137L signaling and acquire the capacity to stimulate T cell proliferation from Day 4 onward. This biphasic activity may contribute to infection-induced T cell attrition, where in the early phase (<24 h) of an infection, massive T cell apoptosis occurs before the antigen-specific T cells expand. © Society for Leukocyte Biology. 2011 Journal Article http://hdl.handle.net/20.500.11937/50933 10.1189/jlb.1010569 Society for Leukocyte Biology restricted |
| spellingShingle | Shaqireen Kwajah, M. Mustafa, N. Holme, A. Pervaiz, Shazib Schwarz, H. Biphasic activity of cd137 ligand-stimulated monocytes on T cell apoptosis and proliferation |
| title | Biphasic activity of cd137 ligand-stimulated monocytes on T cell apoptosis and proliferation |
| title_full | Biphasic activity of cd137 ligand-stimulated monocytes on T cell apoptosis and proliferation |
| title_fullStr | Biphasic activity of cd137 ligand-stimulated monocytes on T cell apoptosis and proliferation |
| title_full_unstemmed | Biphasic activity of cd137 ligand-stimulated monocytes on T cell apoptosis and proliferation |
| title_short | Biphasic activity of cd137 ligand-stimulated monocytes on T cell apoptosis and proliferation |
| title_sort | biphasic activity of cd137 ligand-stimulated monocytes on t cell apoptosis and proliferation |
| url | http://hdl.handle.net/20.500.11937/50933 |