title: Single-cell cytokine analysis of gamma delta T cell responses to nonpeptide mycobacterial antigens.
abstract: TCR gamma delta T cells are considered important in the rapid immune response to intracellular infection. We investigated the early response of peripheral blood gamma delta T cells to the nonpeptide Ag isopentenyl pyrophosphate and to its synthetic analogue ethyl pyrophosphate. In healthy donors, an increase in the number of gamma delta T cells was detected as soon as 4 days after stimulation with the nonpeptide Ags. Single-cell analysis of cytokine production was performed by intracellular staining of IFN-gamma and IL-4. gamma delta T cells were found to rapidly expand and produce IFN-gamma in response to nonpeptide Ags. Furthermore, IL-12 augmented the IFN-gamma response. In contrast, gamma delta T cells from the majority of HIV+ donors did not expand or express IFN-gamma in response to nonpeptide Ags, even in the presence of IL-12. These findings indicate a role for nonpeptide-reactive gamma delta T cells in effective cell-mediated immunity for intracellular pathogens.
authors.affiliation: Division of Dermatology, University of California Los Angeles School of Medicine, 90095, USA.
authors.forename: V E
authors.initials: VE
authors.lastname: García
authors.forename: P A
authors.initials: PA
authors.lastname: Sieling
authors.forename: J
authors.initials: J
authors.lastname: Gong
authors.forename: P F
authors.initials: PF
authors.lastname: Barnes
authors.forename: K
authors.initials: K
authors.lastname: Uyemura
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: B R
authors.initials: BR
authors.lastname: Bloom
authors.forename: C T
authors.initials: CT
authors.lastname: Morita
authors.forename: R L
authors.initials: RL
authors.lastname: Modlin
mesh_terms: D000942:Antigens, Bacterial / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis* / Q000096:biosynthesis; D006679:HIV Seropositivity / Q000276:immunology; D045782:Hemiterpenes; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D009161:Mycobacterium / Q000276:immunology*; D009943:Organophosphorus Compounds / Q000276:immunology* / Q000494:pharmacology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D045782:Hemiterpenes; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018664:Interleukin-12; C004809:isopentenyl pyrophosphate