title: CD40 ligand trimer enhances the response of CD8+ T cells to Mycobacterium tuberculosis.
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-gamma by increasing the number of IFN-gamma-producing CD8(+) T cells and the amount of IFN-gamma produced per cell. CD40LT-induced IFN-gamma 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-gamma mRNA transcription by binding to the IFN-gamma 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.
authors.affiliation: Department of Microbiology and Immunology and Center for Pulmonary and Infectious Disease Control, University of Texas Health Center, Tyler, TX 75708, USA.
authors.forename: Buka
authors.initials: B
authors.lastname: Samten
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wizel
authors.forename: Homayoun
authors.initials: H
authors.lastname: Shams
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Weis
authors.forename: Peter
authors.initials: P
authors.lastname: Klucar
authors.forename: Shiping
authors.initials: S
authors.lastname: Wu
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Vankayalapati
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Thomas
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okada
authors.forename: Alan M
authors.initials: AM
authors.lastname: Krensky
authors.forename: Peter F
authors.initials: PF
authors.lastname: Barnes
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology*; D023201:CD40 Ligand / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D015846:Monokines / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D015846:Monokines; D011994:Recombinant Proteins; D014157:Transcription Factors; D023201:CD40 Ligand; D007371:Interferon-gamma