title: Multieffector-functional immune responses of HMBPP-specific Vγ2Vδ2 T cells in nonhuman primates inoculated with Listeria monocytogenes ΔactA prfA*.
abstract: Although Listeria monocytogenes can induce systemic infection causing spontaneous abortion, septicemia, and meningitis, studies have not been performed to investigate human anti-L. monocytogenes immune responses, including those of Ag-specific Vγ2Vδ2 T cells, a dominant human γδ T cell subset. L. monocytogenes is the only pathogen known to possess both the mevalonate and non-mevalonate isoprenoid biosynthesis pathways that produce metabolic phosphates or phosphoantigens activating human Vγ2Vδ2 T cells, making it interesting to explore in vivo anti-L. monocytogenes immune responses of Vγ2Vδ2 T cells. In this study, we demonstrated that subclinical systemic L. monocytogenes infection of rhesus macaques via parenteral inoculation or vaccination with an attenuated Listeria strain induced multieffector-functional immune responses of phosphoantigen-specific Vγ2Vδ2 T cells. Subclinical systemic infection and reinfection with attenuated L. monocytogenes uncovered the ability of Vγ2Vδ2 T cells to mount expansion and adaptive or recall-like expansion. Expanded Vγ2Vδ2 T cells could traffic to and accumulate in the pulmonary compartment and intestinal mucosa. Expanded Vγ2Vδ2 T cells could evolve into effector cells producing IFN-γ, TNF-α, IL-4, IL-17, or perforin after L. monocytogenes infection, and some effector Vγ2Vδ2 T cells could coproduce IL-17 and IFN-γ, IL-4 and IFN-γ, or TNF-α and perforin. Surprisingly, in vivo-expanded Vγ2Vδ2 T effector cells in subclinical L. monocytogenes infection could directly lyse L. monocytogenes-infected target cells and inhibit intracellular L. monocytogenes bacteria. Thus, we present the first demonstration, to our knowledge, of multieffector-functional Vγ2Vδ2 T cell responses against L. monocytogenes.
authors: Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, IL 60612, USA.
authors: Bridgett
authors: B
authors: Ryan-Payseur
authors: James
authors: J
authors: Frencher
authors: Ling
authors: L
authors: Shen
authors: Crystal Y
authors: CY
authors: Chen
authors: Dan
authors: D
authors: Huang
authors: Zheng W
authors: ZW
authors: Chen
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D008253:Macaca mulatta; D008565:Membrane Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D010755:Organophosphates / Q000008:administration & dosage / Q000276:immunology*; D010454:Peptide Termination Factors / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: C467061:4-hydroxy-3-methyl-2-butenyl diphosphate; D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; D008565:Membrane Proteins; D010755:Organophosphates; D010454:Peptide Termination Factors; C545356:PrfA protein, Listeria monocytogenes; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014613:Vaccines, Attenuated; C072980:actA protein, Listeria monocytogenes