CD226 (DNAM-1) is involved in lymphocyte function-associated antigen 1 costimulatory signal for naive T cell differentiation and proliferation

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+ h...

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Published inThe Journal of experimental medicine Vol. 198; no. 12; pp. 1829 - 1839
Main Authors Shibuya, Kazuko, Shirakawa, Jun, Kameyama, Tomie, Honda, Shin-Ichiro, Tahara-Hanaoka, Satoko, Miyamoto, Akitomo, Onodera, Masafumi, Sumida, Takayuki, Nakauchi, Hiromitsu, Miyoshi, Hiroyuki, Shibuya, Akira
Format Journal Article
LanguageEnglish
Published United States The Rockefeller University Press 15.12.2003
Subjects
Antigens, Differentiation, T-Lymphocyte - physiology
CD226 antigen
CD4 antigen
CD8 antigen
Cell Differentiation
Cell Division
Gene Transfer, Horizontal
Genetic Vectors
Humans
Interleukin-12 - physiology
Interleukin-2 - pharmacology
Lentivirus - genetics
LFA-1 antigen
lipid rafts
Lymphocyte Activation
Lymphocyte Function-Associated Antigen-1 - physiology
Membrane Microdomains - physiology
T-Lymphocytes - physiology
Th1 Cells - physiology
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Summary: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.
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H. Nakauchi's present address is Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Address correspondence to Akira Shibuya, Laboratory for Immune Receptor, RIKEN Research Center for Allergy and Immunology, 3-1-1 Koyadai, Ibaraki 305-0074, Japan. Phone: 81-298-36-9174; Fax: 81-298-36-9175; email: ashibuya@rtc.riken.go.jp
Abbreviations used in this paper: CB, cord blood; cPPT, central polypurine tract; CTS, central termination sequence; ICAM, intercellular adhesion molecule; IRES, internal ribosome entry site; MβCD, methyl-β-cyclodextrin; MOI, multiplicity of infection; PB, peripheral blood; SIN, self-inactivating; WPRE, woodchuck hepatitis virus posttranscriptional regulatory element.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20030958