CD226 (DNAM-1) Is Involved in Lymphocyte Function–associated Antigen 1 Costimulatory Signal for Naive T Cell Differentiation and Proliferation
| Autor: | Akitomo Miyamoto, Masafumi Onodera, Kazuko Shibuya, Tomie Kameyama, Shin-ichiro Honda, Takayuki Sumida, Satoko Tahara-Hanaoka, Akira Shibuya, Hiroyuki Miyoshi, Hiromitsu Nakauchi, Jun Shirakawa |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte Naive T cell Gene Transfer Horizontal Leukocyte adhesion molecule T-Lymphocytes Immunology Genetic Vectors Biology Lymphocyte Activation Article Interleukin 21 Membrane Microdomains Immunology and Allergy Cytotoxic T cell Humans Lymphocyte function-associated antigen 1 lentiviral vector Lentivirus CD28 hemic and immune systems Cell Differentiation Th1 Cells Interleukin-12 Lymphocyte Function-Associated Antigen-1 Cell biology CD226 naive T cells Interleukin 12 ComputingMethodologies_DOCUMENTANDTEXTPROCESSING Interleukin-2 costimulatory molecules CD8 Cell Division LFA-1 |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Popis: | application/pdf 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. |
| Databáze: | OpenAIRE |
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