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-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.
Samten
Buka
B
Department of Microbiology and Immunology and Center for Pulmonary and Infectious Disease Control, University of Texas Health Center, Tyler, TX 75708, USA.
Wizel
Benjamin
B
Shams
Homayoun
H
Weis
Stephen E
SE
Klucar
Peter
P
Wu
Shiping
S
Vankayalapati
Ramakrishna
R
Thomas
Elaine K
EK
Okada
Satoshi
S
Krensky
Alan M
AM
Barnes
Peter F
PF
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
D000276:Adjuvants, Immunologic; D015846:Monokines; D011994:Recombinant Proteins; D014157:Transcription Factors; D023201:CD40 Ligand; D007371:Interferon-gamma