Synergy between CD28 and CD9 costimulation for naive T-cell activation

Immunol Lett. 1997 Jun;58(1):19-23. doi: 10.1016/s0165-2478(97)02706-5.


Our previous study demonstrated that CD9 is expressed on most mature naive T-cells and delivers a potent costimulatory signal that functions independently of CD28. Here, we investigated whether this CD9-mediated signal is different from the CD28-mediated signal in the mode of costimulation and whether both signals function synergistically for T-cell activation. Anti-CD9 or anti-CD28 monoclonal antibody (mAb) increased [3H]TdR incorporation of naive T-cells in the absence of antigen-presenting cells (APC) when coimmobilized with submitogenic doses of anti-CD3 mAb. The levels of costimulation induced by ligation of CD9 and CD28 were comparable. However, the costimulatory effect differed between soluble anti-CD9 and CD28 mAb. A soluble form of anti-CD28 mAb could costimulate anti-CD3-triggered T-cells, whereas soluble anti-CD9 mAb failed to costimulate. Although anti-CD28 costimulated naive T-cells treated with phorbol myristate acetate (PMA) instead of anti-CD3 mAb, a combination of PMA plus anti-CD9 mAb could not induce T-cell activation. The combined costimulation of anti-CD3-triggered T-cells with anti-CD9 and anti-CD28 mAbs resulted in strikingly enhanced [3H]TdR uptake and lymphokine (IL-2 and IFN-gamma) production when compared to those induced by each costimulation. These results suggest that CD9 and CD28 induce T-cell costimulation using different signaling pathways, thereby inducing synergy in T-cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD / immunology*
  • CD28 Antigens / immunology*
  • CD3 Complex / immunology
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Lymph Nodes / cytology
  • Lymphocyte Activation / immunology*
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tetraspanin 29


  • Antibodies, Monoclonal
  • Antigens, CD
  • CD28 Antigens
  • CD3 Complex
  • Cd9 protein, mouse
  • Interleukin-2
  • Membrane Glycoproteins
  • Tetraspanin 29
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate