First Author | Greenwald RJ | Year | 2001 |
Journal | Immunity | Volume | 14 |
Issue | 2 | Pages | 145-55 |
PubMed ID | 11239447 | Mgi Jnum | J:110446 |
Mgi Id | MGI:3640240 | Doi | 10.1016/s1074-7613(01)00097-8 |
Citation | Greenwald RJ, et al. (2001) CTLA-4 regulates induction of anergy in vivo. Immunity 14(2):145-55 |
abstractText | 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. |