RRC ID 54575
Author Shibuya K, Shirakawa J, Kameyama T, Honda S, Tahara-Hanaoka S, Miyamoto A, Onodera M, Sumida T, Nakauchi H, Miyoshi H, Shibuya A.
Title CD226 (DNAM-1) is involved in lymphocyte function-associated antigen 1 costimulatory signal for naive T cell differentiation and proliferation.
Journal J Exp Med
Abstract Upon antigen recognition by the T cell receptor, lymphocyte function-associated antigen 1 (LFA-1) physically associates with the leukocyte adhesion molecule CD226 (DNAM-1) and the protein tyrosine kinase Fyn. We show that lentiviral vector-mediated mutant (Y-F322) CD226 transferred into naive CD4+ helper T cells (Ths) inhibited interleukin (IL)-12-independent Th1 development initiated by CD3 and LFA-1 ligations. Moreover, proliferation induced by LFA-1 costimulatory signal was suppressed in mutant (Y-F322) CD226-transduced naive CD4+ and CD8+ T cells in the absence of IL-2. These results suggest that CD226 is involved in LFA-1-mediated costimulatory signals for triggering naive T cell differentiation and proliferation. We also demonstrate that although LFA-1, CD226, and Fyn are polarized at the immunological synapse upon stimulation with anti-CD3 in CD4+ and CD8+ T cells, lipid rafts are polarized in CD4+, but not CD8+, T cells. Moreover, proliferation initiated by LFA-1 costimulatory signal is suppressed by lipid raft disruption in CD4+, but not CD8+, T cells, suggesting that the LFA-1 costimulatory signal is independent of lipid rafts in CD8+ T cells.
Volume 198(12)
Pages 1829-39
Published 2003-12-15
DOI 10.1084/jem.20030958
PII jem.20030958
PMID 14676297
PMC PMC2194159
MeSH Antigens, Differentiation, T-Lymphocyte / physiology* Cell Differentiation Cell Division Gene Transfer, Horizontal Genetic Vectors Humans Interleukin-12 / physiology Interleukin-2 / pharmacology Lentivirus / genetics Lymphocyte Activation Lymphocyte Function-Associated Antigen-1 / physiology* Membrane Microdomains / physiology T-Lymphocytes / physiology* Th1 Cells / physiology
IF 10.892
Times Cited 151
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The most frequently cited source Patent(IFI CLAIMS)
Total number of mentions 17
Altmetric score changes over past 6months 0.0
Resource
DNA material CS-CDF-CG-PRE (RDB04379)