Le et al. showed that following attenuated Plasmodium sporozoite vaccination, WT, but not TCRγδ KO mice accumulated antigen-specific T cells in their livers and spleens. Antibody blockade of Vγ1+γδ T cells before/soon after vaccination impaired response, and Vγ1+γδ splenic T cells increased after vaccination of WT mice. Vγ1+γδ T cell-derived IL-4 synergized with IFNγ (likely T cell-derived) and CD4+ T cell-derived CD40L to signal cDC1s to produce IL-12. IL-12 and IL-4 induced CD8+ T cells to upregulate IL-12R and expand/differentiate into protective liver TRM cells. PMA induced IL-4 production from human Vδ2+γδ peripheral blood T cells from individuals with uncomplicated P. falciparum malaria infection.
Contributed by Paula Hochman
ABSTRACT: Dendritic cells (DCs) are pivotal for initiating adaptive immunity, a process triggered by the activation of DCs via pathogen products or damage. Immunization with sporozoites from Plasmodium leads to CD8+ T cell priming in a response initiated by collaboration between conventional type 1 DCs (cDC1s) and γδ T cells. Here we show that Vγ1+ γδ T cells have an initiating role by directly supplying interleukin-4 (IL-4). IL-4 and interferon-γ (IFNγ) synergize with CD4+ T cell-derived CD40L to induce IL-12 production by cDC1. Both IL-12 and IL-4 then directly signal responding CD8+ T cells and drive enhanced IL-12 receptor expression and expansion. This study shows how Vγ1+ γδ T cells can initiate CD8+ T cell immunity to Plasmodium and that responses to some pathogens require help from innate-like T cells to pass an initiation threshold and further amplify the response in a process underscored by IL-4 production.
Author Info: (1) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. (2) Burnet Instit
Author Info: (1) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. (2) Burnet Institute, Life Science Division, Melbourne, Victoria, Australia. (3) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. (4) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. (5) Melbourne Bioinformatics, University of Melbourne, Parkville, Victoria, Australia. (6) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. (7) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. (8) School of Biosciences, University of Melbourne, Parkville, Victoria, Australia. (9) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. (10) School of Biosciences, University of Melbourne, Parkville, Victoria, Australia. (11) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. (12) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. (13) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. (14) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. Computational Sciences Initiative, Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia. (15) Burnet Institute, Life Science Division, Melbourne, Victoria, Australia. Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia. (16) Burnet Institute, Life Science Division, Melbourne, Victoria, Australia. (17) Menzies School of Health Research-National Institute of Health Research and Development Malaria Research Program, Timika, Indonesia. District Health Authority, Timika, Indonesia. (18) Infection and Immunity Program, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Bundoora, Victoria, Australia. Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, Victoria, Australia. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia. (19) Division of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia. (20) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. (21) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. (22) School of Biosciences, University of Melbourne, Parkville, Victoria, Australia. (23) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. School of Biomedical Sciences, Faculty of Medicine & Health, and the UNSW RNA Institute, The University of New South Wales, Kensington, New South Wales, Australia. (24) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. Burnet Institute, Life Science Division, Melbourne, Victoria, Australia. Menzies School of Health Research-National Institute of Health Research and Development Malaria Research Program, Timika, Indonesia. (25) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. (26) Department of Microbiology and Immunology and The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. lynette.beattie@unimelb.edu.au.
