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4‐1BB enhances CD8 + T cell expansion by regulating cell cycle progression through changes in expression of cyclins D and E and cyclin‐dependent kinase inhibitor p27 kip1
Author(s) -
Lee HyeonWoo,
Nam KyungOk,
Park SuJung,
Kwon Byoung S.
Publication year - 2003
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200323996
Subject(s) - cyclin d2 , cyclin d , biology , cyclin a , cyclin a2 , microbiology and biotechnology , cyclin e , cyclin d3 , cyclin , cyclin dependent kinase , cyclin b , pi3k/akt/mtor pathway , cell cycle , cancer research , kinase , cyclin dependent kinase 2 , signal transduction , protein kinase a , cell , biochemistry
Abstract The T cell costimulatory receptor 4‐1BB enhances cell cycle progression and proliferation of CD8 + T cells in both an IL‐2‐dependent and ‐independent manner. In these studies, 4‐1BB costimulation was shown to increase cyclin D2, D3, and E expression, and concomitantly down‐regulate the expression of the cyclin‐dependent kinase inhibitor p27 kip1 . 4‐1BB increases cyclin D2 transcription via mitogen‐activated/extracellular signal‐regulated kinase‐1/2 and LY294002‐sensitive phosphatidylinositol 3‐kinase (PI3K) signaling pathways. In addition, 4‐1BB up‐regulates cyclin D2 translation via PI3K/Akt/mammalian target of rapamycin (mTOR) pathways, presumably triggered by IL‐2/IL‐2 receptor ligation. The enhanced cyclin D2 and D3 expression initiates up‐regulation of cyclin E expression and down‐regulation of p27 kip1 . Our results suggest a role for cyclin D2, D3, and E, and p27 kip1 proteins in the 4‐1BB‐mediated cell cycle progression of CD8 + T cells in vivo .