| First Author | Zhang R | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 8 | Pages | 5331-9 |
| PubMed ID | 18832689 | Mgi Jnum | J:140769 |
| Mgi Id | MGI:3814520 | Doi | 10.4049/jimmunol.181.8.5331 |
| Citation | Zhang R, et al. (2008) Casitas B-lineage lymphoma b inhibits antigen recognition and slows cell cycle progression at late times during CD4+ T cell clonal expansion. J Immunol 181(8):5331-9 |
| abstractText | Optimal clonal expansion of CD4(+) T cells during the primary response to Ag requires prolonged TCR recognition of peptide Ag/MHC complexes. In this study, we investigated the capacity of Casitas B-lineage lymphoma b (Cbl-b) to counter-regulate late TCR signals necessary for continued cell division in vivo. During the first 24 h of a primary response to Ag, Cblb(-/-) 5C.C7 CD4(+) T cells demonstrated no alteration in CD69, CD25, and CD71 up-regulation or cell growth as compared with wild-type cells. Nevertheless, beyond 24 h, both the expression of CD71 and the rate of cell division were increased in the genetic absence of Cbl-b, leading to an augmented clonal expansion. This deregulation of late T cell proliferation in the absence of Cbl-b resulted in part from an inability of Cblb(-/-) T cells to desensitize Akt, PLCgamma-1, and ERK phosphorylation events downstream of the TCR/CD3 complex, in addition to their failure to undergo a growth arrest in the absence of Ag. These observations now suggest a novel role for Cbl-b in triggering the exit from cell cycle at the end of a CD4(+) T cell clonal expansion. |
