title: Th17-related cytokines contribute to recall-like expansion/effector function of HMBPP-specific Vγ2Vδ2 T cells after Mycobacterium tuberculosis infection or vaccination.
abstract: Whether cytokines can influence the adaptive immune response by antigen-specific γδ T cells during infections or vaccinations remains unknown. We previously demonstrated that, during BCG/Mycobacterium tuberculosis (Mtb) infections, Th17-related cytokines markedly upregulated when phosphoantigen-specific Vγ2Vδ2 T cells expanded. In this study, we examined the involvement of Th17-related cytokines in the recall-like responses of Vγ2Vδ2 T cells following Mtb infection or vaccination against TB. Treatment with IL-17A/IL-17F or IL-22 expanded phosphoantigen 4-hydroxy-3-methyl-but-enyl pyrophosphate (HMBPP)-stimulated Vγ2Vδ2 T cells from BCG-vaccinated macaques but not from naïve animals, and IL-23 induced greater expansion than the other Th17-related cytokines. Consistently, Mtb infection of macaques also enhanced the ability of IL-17/IL-22 or IL-23 to expand HMBPP-stimulated Vγ2Vδ2 T cells. When evaluating IL-23 signaling as a prototype, we found that HMBPP/IL-23-expanded Vγ2Vδ2 T cells from macaques infected with Mtb or vaccinated with BCG or Listeria ΔactA prfA*-ESAT6/Ag85B produced IL-17, IL-22, IL-2, and IFN-γ. Interestingly, HMBPP/IL-23-induced production of IFN-γ in turn facilitated IL-23-induced expansion of HMBPP-activated Vγ2Vδ2 T cells. Furthermore, HMBPP/IL-23-induced proliferation of Vγ2Vδ2 T cells appeared to require APC contact and involve the conventional and novel protein kinase C signaling pathways. These findings suggest that Th17-related cytokines can contribute to recall-like expansion and effector function of Ag-specific γδ T cells after infection or vaccination.
authors.affiliation: Chinese Academy of Science, Institut Pasteur of Shanghai, Shanghai, China; Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, IL, USA.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Shen
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Wang
authors.forename: Crystal Y
authors.initials: CY
authors.lastname: Chen
authors.forename: James
authors.initials: J
authors.lastname: Frencher
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Enzhuo
authors.initials: E
authors.lastname: Yang
authors.forename: Bridgett
authors.initials: B
authors.lastname: Ryan-Payseur
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D008087:Listeria / Q000276:immunology; D008252:Macaca fascicularis; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010755:Organophosphates / Q000276:immunology / Q000494:pharmacology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D014611:Vaccination; D000097043:Interleukin-22
chemical_list: D001428:Bacterial Vaccines; D007371:Interferon-gamma; D020381:Interleukin-17; D007376:Interleukin-2; D053759:Interleukin-23; D007378:Interleukins; D010755:Organophosphates; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins; D000097043:Interleukin-22; C467061:4-hydroxy-3-methyl-2-butenyl diphosphate
keywords: IL-17/IL-22; IL-23; Phosphoantigen; Tuberculosis; γδ T cells