Antagonistic roles for CTLA-4 and the mammalian target of rapamycin in the regulation of clonal anergy: Enhanced cell cycle progression promotes recall antigen responsiveness

T. L. Vanasek, Alexander Khoruts, T. Zell, Daniel L Mueller

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

CD4+ T cells that undergo multiple rounds of cell division during primary Ag challenge in vivo produce IL-2 on secondary Ag rechallenge, whereas cells that fail to progress through the cell cycle are anergic to restimulation. Anti-CTLA-4 mAb treatment during primary Ag exposure increases cell cycle progression and enhances recall Ag responsiveness; however, simultaneous treatment with rapamycin, an inhibitor of the mammalian target of rapamycin and potent antiproliferative agent, prevents both effects. The data suggest that cell cycle progression plays a primary role in the regulation of recall Ag responsiveness in CD4+ T cells in vivo. CTLA-4 molecules promote clonal anergy development only indirectly by limiting cell cycle progression during the primary response.

Original languageEnglish (US)
Pages (from-to)5636-5644
Number of pages9
JournalJournal of Immunology
Volume167
Issue number10
DOIs
StatePublished - Nov 15 2001

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