CD40 ligand trimer enhances the response of CD8+ T cells to Mycobacterium tuberculosis.

We investigated the effect of recombinant CD40 ligand trimer (CD40LT) on the functional capacity of peripheral blood CD8 + T cells from healthy tuberculin reactors that were cultured with Mycobacterium tuberculosis -infected autologous monocytes. CD40LT enhanced the capacity of M. tuberculosis -responsive CD8 + T cells to produce IFN-γ by increasing the number of IFN-γ-producing CD8 + T cells and the amount of IFN-γ produced per cell. CD40LT-induced IFN-γ production was dependent on production of IL-12 and IL-18, but did not require IL-15. CD40LT up-regulated expression of the transcription factors phosphorylated CREB and c-Jun, both of which have been previously shown to stimulate IFN-γ mRNA transcription by binding to the IFN-γ promoter. CD40LT also enhanced the capacity of CD8 + T cells to lyse M. tuberculosis -infected monocytes, and increased CTL activity was associated with higher expression of perforin and granulysin, but not of Fas ligand. We conclude that CD40LT can enhance CD8 + T cell effector function in response to M. tuberculosis .