CTLA-4-Mediated inhibition of early events of T cell proliferation.

Published

Journal Article

CTLA-4 engagement by mAbs inhibits, while CD28 enhances, IL-2 production and proliferation upon T cell activation. Here, we have analyzed the mechanisms involved in CTLA-4-mediated inhibition of T cell activation of naive CD4+ T cells using Ab cross-linking. CTLA-4 ligation inhibited CD3/CD28-induced IL-2 mRNA accumulation by inhibiting IL-2 transcription, which appears to be mediated in part through decreasing NF-AT accumulation in the nuclei. However, CTLA-4 ligation did not appear to affect the CD28-mediated stabilization of IL-2 mRNA. Further, CTLA-4 engagement inhibited progression through the cell cycle by inhibiting the production of cyclin D3, cyclin-dependent kinase (cdk)4, and cdk6 when the T cells were stimulated with anti-CD3/CD28 and with anti-CD3 alone. These results indicate that CTLA-4 signaling inhibits events early in T cell activation both at IL-2 transcription and at the level of IL-2-independent events of the cell cycle, and does not simply oppose CD28-mediated costimulation.

Full Text

Duke Authors

Cited Authors

  • Brunner, MC; Chambers, CA; Chan, FK; Hanke, J; Winoto, A; Allison, JP

Published Date

  • May 15, 1999

Published In

Volume / Issue

  • 162 / 10

Start / End Page

  • 5813 - 5820

PubMed ID

  • 10229815

Pubmed Central ID

  • 10229815

International Standard Serial Number (ISSN)

  • 0022-1767

Language

  • eng

Conference Location

  • United States