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

The role of CD40 ligand (CD40L) in CD8 T cell activation was assessed by tr acking antigen-specific T cells in vivo using both adoptive transfer of T c ell 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 occurr ed after adoptive transfer to CD40L-deficient mice. However, mucosal CDS T cells in normal and CD40(-/-) mice were equivalent killers, indicating that CD40L was not required for CTL differentiation. Appearance of virus-specif ic mucosal, but not splenic, CD8 cells also relied heavily on CD40-CD40L in teractions. The mucosal C-TL response of transferred CD8 T cells was MHC cl ass II and interleukin 12 independent. The results established a novel path way of direct CD40L-mediated CD8 T cell activation.