CD28-mediated induction of proliferation in resting T cells in vitro and in vivo without engagement of the T cell receptor: evidence for functionally distinct forms of CD28

Eur J Immunol. 1997 Jan;27(1):239-47. doi: 10.1002/eji.1830270136.


JJ316 and JJ319 are rat CD28-specific monoclonal antibodies (mAb) of the gamma1 kappa isotype with identical co-stimulatory potency. At a concentration 100-1000-fold higher than that required for co-stimulation, JJ316, but not JJ319 induces massive proliferation of all T cell subsets in vitro without T cell receptor (TCR) triggering. "Direct" stimulation by JJ316 is fully blocked by JJ319, indicating that it is not due to cross-reactivity of JJ316 with the TCR complex or other activating receptors. JJ316 binds much more slowly to primary T cells than JJ319, whereas both antibodies bind with similar kinetics to CD28-transfected L-929 cells, suggesting that JJ316 binding to T cells requires redistribution or a conformational change of CD28. In vivo, JJ316 but not JJ319 induces rapid and transient proliferation of most CD4 T cells and, indirectly, of B cells. These data show that TCR engagement is not an absolute prerequisite either in vitro or in vivo for the induction of T cell proliferation through CD28 and suggest that mAb JJ316 is able to stimulate resting T cells directly by recruiting CD28 molecules from an inactive to an active form.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Antigens, CD / physiology
  • B7-1 Antigen / physiology
  • B7-2 Antigen
  • CD28 Antigens / physiology*
  • Cell Division
  • Female
  • Kinetics
  • Lymph Nodes / cytology
  • Lymphocyte Activation*
  • Lymphocyte Subsets / immunology
  • Male
  • Membrane Glycoproteins / physiology
  • Rats
  • Rats, Inbred Lew
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction
  • Spleen / cytology
  • T-Lymphocytes / physiology*


  • Antibodies, Monoclonal
  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CD28 Antigens
  • Cd86 protein, rat
  • JJ 316
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell