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
|
Resource |
DNA material |
CS-CDF-CG-PRE (RDB04379) |