Journal
IMMUNITY
Volume 14, Issue 2, Pages 145-155Publisher
CELL PRESS
DOI: 10.1016/S1074-7613(01)00097-8
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Funding
- NHLBI NIH HHS [T32HL07627] Funding Source: Medline
- NIAID NIH HHS [AI40614, AI41584, AI43552, AI35297, F32AI10415] Funding Source: Medline
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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 p27(kip1), 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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