TY - JOUR
T1 - Casitas B-lineage lymphoma b inhibits antigen recognition and slows cell cycle progression at late times during CD4+ T cell clonal expansion
AU - Zhang, Ruan
AU - Zhang, Na
AU - Mueller, Daniel L
PY - 2008
Y1 - 2008
N2 - 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, PLCγ-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.
AB - 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, PLCγ-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.
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U2 - 10.4049/jimmunol.181.8.5331
DO - 10.4049/jimmunol.181.8.5331
M3 - Article
C2 - 18832689
AN - SCOPUS:54049108861
SN - 0022-1767
VL - 181
SP - 5331
EP - 5339
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -