Enhancement of BCG-induced Th1 immune response through Vgamma9Vdelta2 T cell activation with non-peptidic drugs.
Since drug-activated gammadelta T cells promote dendritic cell (DC) maturation, we analyzed the effect of combining gammadelta T cell specific drugs with BCG in vitro. BCG-induced DC maturation was increased by bromohydrin-pirophosphate (BrHPP) or zoledronate (Zol)-activated gammadelta T cells. Specifically, the co-culture with activated Vgamma9Vdelta2 T cells with BCG-infected DC resulted in a significant increase of the expression of CD80, CD86, CD40 and CD25 molecules on DC. Moreover, DC were able to produce increased levels of TNF-alpha and synthesize ex novo IL-15 without altering the IL-10/IL-12 immunoregulatory pathway. Finally, the Th1 immunity induced by BCG-infected DC on naïve CD4 T cells was increased by gammadelta T cell activation with BrHpp or Zol. These data indicate that gammadelta T cell triggering drugs could be used to enhance the BCG induced Th1 immunity.
Martino
Angelo
A
Laboratory of Cellular Immunology, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Via Portuense 292, 00149 Rome, Italy. martino@inmi.it
Casetti
Rita
R
Poccia
Fabrizio
F
D000438:Alcohols / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D016753:Interleukin-10 / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology; D008213:Lymphocyte Activation; D009163:Mycobacterium bovis / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000276:immunology / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D000077211:Zoledronic Acid
D000438:Alcohols; D004164:Diphosphonates; D007093:Imidazoles; D019409:Interleukin-15; D016692:Receptors, Antigen, T-Cell, gamma-delta; D032581:Tuberculosis Vaccines; D014409:Tumor Necrosis Factor-alpha; C023963:bromohydrins; D016753:Interleukin-10; D000077211:Zoledronic Acid