Help for cytotoxic-T-cell responses is mediated by CD40 signalling

Nature. 1998 Jun 4;393(6684):478-80. doi: 10.1038/30996.


Cytotoxic T lymphocytes (CTLs) which carry the CD8 antigen recognize antigens that are presented on target cells by the class I major histocompatibility complex. CTLs are responsible for the killing of antigen-bearing target cells, such as virus-infected cells. Although CTL effectors can act alone when killing target cells, their differentiation from naive CD8-positive T cells is often dependent on 'help' from CD4-positive helper T (TH) cells. Furthermore, for effective CTL priming, this help must be provided in a cognate manner, such that both the TH cell and the CTL recognize antigen on the same antigen-presenting cell. One explanation for this requirement is that TH cells are needed to convert the antigen-presenting cell into a cell that is fully competent to prime CTL. Here we show that signalling through CD40 on the antigen-presenting cells can replace the requirement for TH cells, indicating that T-cell 'help', at least for generation of CTLs by cross-priming, is mediated by signalling through CD40 on the antigen-presenting cell.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • CD40 Antigens / immunology*
  • CD40 Ligand
  • In Vitro Techniques
  • Lymphocyte Activation
  • Membrane Glycoproteins / immunology
  • Mice
  • Ovalbumin / immunology
  • Signal Transduction*
  • Spleen / cytology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology


  • CD40 Antigens
  • Membrane Glycoproteins
  • CD40 Ligand
  • Ovalbumin