| First Author | Lee SW | Year | 2005 |
| Journal | J Immunol | Volume | 174 |
| Issue | 11 | Pages | 6803-8 |
| PubMed ID | 15905521 | Mgi Jnum | J:99039 |
| Mgi Id | MGI:3580992 | Doi | 10.4049/jimmunol.174.11.6803 |
| Citation | Lee SW, et al. (2005) Enhanced CD4 T cell responsiveness in the absence of 4-1BB. J Immunol 174(11):6803-8 |
| abstractText | The 4-1BB (CD137) is a member of the TNFR superfamily, and is expressed on several cell types, including activated T cells. Although 4-1BB ligation by agonistic Ab or 4-1BB ligand-expressing APCs can costimulate T cells, the physiological significance of 4-1BB expression in vivo during T cell responses is still being elucidated. In this study, we have addressed the impact on CD4 T cell priming when 4-1BB is absent after gene targeting. Surprisingly, 4-1BB(-/-) mice generated more enhanced effector CD4 T cell responses to OVA protein in adjuvant, even though Ab responses in 4-1BB(-/-) mice were normal. Using an adoptive transfer system with OT-II TCR transgenic CD4 T cells, we found that 4-1BB(-/-) CD4 cells responding in a 4-1BB-sufficient environment had enhanced cell division compared with wild-type cells and displayed augmented clonal expansion during the primary response. This was not due to a developmental defect as 4-1BB-deficient CD4 cells could respond normally to Ag in vitro. These results demonstrate that the absence of 4-1BB can make CD4 T cells hyperresponsive to protein Ag in vivo, suggesting a new unappreciated negative regulatory role of 4-1BB when expressed on a T cell. |
