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

Buka Samten, Benjamin Wizel, Homayoun Shams, Stephen E. Weis, Peter Klucar, Shiping Wu, Ramakrishna Vankayalapati, Elaine K. Thomas, Satoshi Okada, Alan M. Krensky, Peter F. Barnes

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3180-3186
Number of pages7
JournalJournal of Immunology
Volume170
Issue number6
DOIs
StatePublished - 15 Mar 2003

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