title: HMBPP-deficient Listeria mutant immunization alters pulmonary/systemic responses, effector functions, and memory polarization of Vγ2Vδ2 T cells.
abstract: Whereas infection or immunization of humans/primates with microbes coproducing HMBPP/IPP can remarkably activate Vγ2Vδ2 T cells, in vivo studies have not been done to dissect HMBPP- and IPP-driven expansion, pulmonary trafficking, effector functions, and memory polarization of Vγ2Vδ2 T cells. We define these phosphoantigen-host interplays by comparative immunizations of macaques with the HMBPP/IPP-coproducing Listeria ΔactA prfA* and HMBPP-deficient Listeria ΔactA ΔGCPE: prfA* mutant. The HMBPP-deficient ΔGCPE: mutant shows lower ability to expand Vγ2Vδ2 T cells in vitro than the parental HMBPP-producing strain but displays comparably attenuated infectivity or immunogenicity. Respiratory immunization of macaques with the HMBPP-deficient mutant elicits lower pulmonary and systemic responses of Vγ2Vδ2 T cells compared with the HMBPP-producing vaccine strain. Interestingly, HMBPP-deficient mutant reimmunization or boosting elicits enhanced responses of Vγ2Vδ2 T cells, but the magnitude is lower than that by HMBPP-producing listeria. HMBPP-deficient listeria differentiated fewer Vγ2Vδ2 T effector cells capable of coproducing IFN-γ and TNF-α and inhibiting intracellular listeria than HMBPP-producing listeria. Furthermore, HMBPP deficiency in listerial immunization influences memory polarization of Vγ2Vδ2 T cells. Thus, both HMBPP and IPP production in listerial immunization or infection elicit systemic/pulmonary responses and differentiation of Vγ2Vδ2 T cells, but a role for HMBPP is more dominant. Findings may help devise immune intervention.
authors.affiliation: Microbiology and Immunology and Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, Illinois, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Frencher
authors.affiliation: Microbiology and Immunology and Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, Illinois, USA.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Shen
authors.affiliation: Microbiology and Immunology and Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, Illinois, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.affiliation: Pharmacology and.
authors.forename: Jessica O
authors.initials: JO
authors.lastname: Wilson
authors.affiliation: Microbiology and Immunology and.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Freitag
authors.affiliation: Pharmacology and.
authors.forename: Alicia N
authors.initials: AN
authors.lastname: Rizzo
authors.affiliation: Microbiology and Immunology and Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, Illinois, USA.
authors.forename: Crystal Y
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Microbiology and Immunology and Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, Illinois, USA zchen@uic.edu.
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics; D001428:Bacterial Vaccines / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D004798:Enzymes / Q000172:deficiency / Q000235:genetics; D007114:Immunization; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008089:Listeria monocytogenes / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000276:immunology* / Q000517:prevention & control; D008168:Lung / Q000276:immunology*; D008253:Macaca mulatta; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010755:Organophosphates / Q000276:immunology*; D010454:Peptide Termination Factors / Q000172:deficiency / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014613:Vaccines, Attenuated / Q000276:immunology; D014774:Virulence / Q000235:genetics
chemical_list: C467061:4-hydroxy-3-methyl-2-butenyl diphosphate; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D016207:Cytokines; D004798:Enzymes; D010755:Organophosphates; D010454:Peptide Termination Factors; C545356:PrfA protein, Listeria monocytogenes; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D014613:Vaccines, Attenuated; C421242:hydroxymethylbutenyl 4-diphosphate synthase; D007371:Interferon-gamma
keywords: T cells; antigen; cell activation; lung; memory response
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