B7/CD28-dependent and -independent induction of CD40 ligand expression

J Immunol. 1995 Dec 1;155(11):5124-32.

Abstract

The induction of a T cell-dependent Ab response is mediated by the interaction of the T cell activation Ag, CD40 ligand (CD40L), with CD40. Since this interaction is independent of Ag, coreceptors such as CD4, and MHC molecules, the expression of the CD40L must be strictly regulated or B cell-mediated autoimmunity may be produced. In this study, we examined the requirements for costimulatory signals for induction of CD40L expression in vitro and in vivo on CD4+ T cells from normal and CD28-deficient mice following stimulation with anti-CD3, Con A, or specific peptide Ag. Expression of B7-1 was both necessary and sufficient for induction of the CD40L on normal CD4+ T cells when L cell transfectants were used as APCs. When normal accessory cell populations were used, only partial inhibition of induction of the CD40L was observed with reagents that inhibit B7/CD28 interactions. Furthermore, the CD40L could be induced on CD4+ T cells from CD28-deficient mice. Thus, non-B7/CD28 cellular interactions can also mediate the costimulatory signals needed for induction of CD40L expression.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • B7-1 Antigen / physiology*
  • Base Sequence
  • CD28 Antigens / physiology*
  • CD3 Complex / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD40 Ligand
  • Cells, Cultured
  • Female
  • Lymph Nodes / cytology
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Signal Transduction
  • Spleen / cytology

Substances

  • Antibodies, Monoclonal
  • B7-1 Antigen
  • CD28 Antigens
  • CD3 Complex
  • Membrane Glycoproteins
  • CD40 Ligand