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

J Exp Med. 2003 Dec 15;198(12):1829-39. doi: 10.1084/jem.20030958.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • CD226 antigen
  • Interleukin-2
  • Lymphocyte Function-Associated Antigen-1
  • Interleukin-12