A fundamental difference in the capacity to induce proliferation of naive T cells between CD28 and other co-stimulatory molecules

Eur J Immunol. 1998 Mar;28(3):926-35. doi: 10.1002/(SICI)1521-4141(199803)28:03<926::AID-IMMU926>3.0.CO;2-0.


T cell activation requires two signals: a signal from the TCR and a co-stimulatory signal provided by antigen-presenting cells (APC). In addition to CD28, multiple molecules on the T cell have been described to deliver co-stimulatory signals. Here, we investigated whether there exist quantitative or qualitative differences in the co-stimulatory capacity between CD28 and other molecules. Anti-CD28 monoclonal antibody (mAb) and mAb against CD5, CD9, CD2, CD44 or CD11a all induced activation of naive T cells in the absence of APC when co-immobilized with a submitogenic dose of anti-CD3 mAb. [3H]Thymidine incorporation determined 2 days after co-stimulation was all comparable. In contrast to progressive T cell proliferation induced by CD28 co-stimulation, co-stimulation by other T cell molecules led to a decrease in viable cell recovery along with the induction of apoptosis of once activated T cells. This was associated with a striking difference in IL-2 production; CD28 co-stimulation induced progressively increasing IL-2 production, whereas co-stimulation by other molecules produced limited amounts of IL-2. Addition of recombinant IL-2 to the latter cultures corrected the induction of apoptosis, resulting in levels of cellular proliferation comparable to those observed for CD28 co-stimulation. These results indicate that a fundamental difference exists in the nature of co-stimulation between CD28 and other molecules, which can be evaluated by the levels of IL-2 production, but not simply by [3H]thymidine incorporation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / physiology
  • Apoptosis
  • CD2 Antigens / physiology
  • CD28 Antigens / physiology*
  • CD3 Complex / physiology
  • CD5 Antigens / physiology
  • Cell Cycle
  • Hyaluronan Receptors / physiology
  • Integrin beta1 / physiology
  • Interleukin-2 / pharmacology
  • Lymphocyte Activation*
  • Lymphocyte Function-Associated Antigen-1 / physiology
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred BALB C
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • Tetraspanin 29


  • Antigens, CD
  • CD2 Antigens
  • CD28 Antigens
  • CD3 Complex
  • CD5 Antigens
  • Cd9 protein, mouse
  • Hyaluronan Receptors
  • Integrin beta1
  • Interleukin-2
  • Lymphocyte Function-Associated Antigen-1
  • Membrane Glycoproteins
  • Tetraspanin 29