[HTML][HTML] CTLA-4 regulates induction of anergy in vivo

RJ Greenwald, VA Boussiotis, RB Lorsbach, AK Abbas… - Immunity, 2001 - cell.com
RJ Greenwald, VA Boussiotis, RB Lorsbach, AK Abbas, AH Sharpe
Immunity, 2001cell.com
The requirement for CTLA-4 during the induction of peripheral T cell tolerance in vivo was
investigated using naive TCR transgenic T cells lacking CTLA-4. CTLA-4−/− T cells are
resistant to tolerance induction, as demonstrated by their proliferative responses, IL-2
production, and progression into the cell cycle. Following exposure to a tolerogenic stimulus
in vivo and restimulation in vitro, wild-type T cells are blocked at the late G1 to S restriction
point of the cell cycle. In contrast, CTLA-4−/− T cells enter into the S phase of the cell cycle …
Abstract
The requirement for CTLA-4 during the induction of peripheral T cell tolerance in vivo was investigated using naive TCR transgenic T cells lacking CTLA-4. CTLA-4−/− T cells are resistant to tolerance induction, as demonstrated by their proliferative responses, IL-2 production, and progression into the cell cycle. Following exposure to a tolerogenic stimulus in vivo and restimulation in vitro, wild-type T cells are blocked at the late G1 to S restriction point of the cell cycle. In contrast, CTLA-4−/− T cells enter into the S phase of the cell cycle, as shown by downregulation of p27kip1, elevated cdk2 kinase activity, and Rb hyperphosphorylation. Thus, CTLA-4 has an essential role in determining the outcome of T cell encounter with a tolerogenic stimulus.
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