A critical role for CD40-CD40 ligand interactions in amplification of the mucosal CD8 T cell response

Leo Lefrançois, Sara Olson, David Masopust

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


The role of CD40 ligand (CD40L) in CD8 T cell activation was assessed by tracking antigen-specific T cells in vivo using both adoptive transfer of T cell receptor transgenic T cells and major histocompatibility complex (MHC) class I tetramers. Soluble antigen immunization induced entry of CD8 cells into the intestinal mucosa and cytotoxic T lymphocyte (CTL) differentiation, whereas CD8 cells in secondary lymphoid tissue proliferated but were not cytolytic. Immunization concurrent with CD40L blockade or in the absence of CD40 demonstrated that accumulation of CD8 T cells in the mucosa was CD40L dependent. Furthermore, activation was mediated through CD40L expressed by the CD8 cells, since inhibition by anti-CD40L monoclonal antibodies occurred after adoptive transfer to CD40L-deficient mice. However, mucosal CD8 T cells in normal and CD40(-/-) mice were equivalent killers, indicating that CD40L was not required for CTL differentiation. Appearance of virus-specific mucosal, but not splenic, CD8 cells also relied heavily on CD40-CD40L interactions. The mucosal CTL response of transferred CD8 T cells was MHC class II and interleukin 12 independent. The results established a novel pathway of direct CD40L-mediated CD8 T cell activation.

Original languageEnglish (US)
Pages (from-to)1275-1283
Number of pages9
JournalJournal of Experimental Medicine
Issue number9
StatePublished - Nov 1 1999


  • CD40
  • CD8
  • Costimulation
  • Mucosa
  • Virus


Dive into the research topics of 'A critical role for CD40-CD40 ligand interactions in amplification of the mucosal CD8 T cell response'. Together they form a unique fingerprint.

Cite this