Joag et al. demonstrated that systemic T cell-based vaccines generate robust T cell surveillance throughout the body, integrating cellular and humoral immunity. Intravenous heterologous prime-boost vaccination in macaques established SIV-gag–specific CD8⁺ memory (including resident memory [Trm]), T cells across more than 30 lymphoid, mucosal, and visceral tissues. Local Trm reactivation in the reproductive tract mucosa activated stromal, endothelial, and innate lymphoid cells, amplifying interferon-driven antiviral programs. These signals recruited CD4⁺ T cells with host-defense signatures, and mobilized B and plasma cells.
Contributed by Shishir Pant
ABSTRACT: CD8(+) resident memory T (Trm) cells comprise a small population of frontline sentinels compared with the large tissues they surveil, making outsized contributions to immune protection from infection. Here, we interrogated mechanisms of Trm cell function in primates. Intravenous immunization of macaques with a simian immunodeficiency virus (SIV)-gag-containing heterologous prime-boost-boost vaccine established memory T cells in >30 tissues, including visceral and mucosal compartments. Upon in vivo reactivation in the reproductive tract, antigen-sensing CD8(+) Trm activated local stromal, parenchymal, and innate and adaptive immune cells. Stromal and parenchymal cells accentuated leukocyte migration and antiviral defenses. B and plasma cells mobilized into the vaginal mucosa, and bloodborne CD4(+) T cells were recruited and adopted a host-defense program. Our findings demonstrate that systemic vaccination promotes a Trm cell response in barrier compartments and that Trm cells repurpose abundant neighboring stromal, parenchymal, and immune cells to amplify alarm signals and activate diverse host defenses.
Author Info: (1) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: vineet.joag@seattlechildrens.org. (2)
Author Info: (1) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: vineet.joag@seattlechildrens.org. (2) Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA. (3) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. (4) Department of Microbiology and Immunology, Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30322, USA. (5) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. (6) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. (7) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. (8) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. (9) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. (10) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. (11) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. (12) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. (13) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. (14) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. (15) Department of Microbiology and Immunology, Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30322, USA. (16) Department of Microbiology and Immunology, Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30322, USA. (17) Department of Pathology and Laboratory Medicine, Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA, USA. (18) Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6G 2V4, Canada. (19) Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. (20) Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. (21) Department of Medicine, Division of Rheumatic and Autoimmune Diseases, University of Minnesota, Minneapolis, MN, USA. (22) Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA. (23) Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA. (24) Department of Pathology and Laboratory Medicine, Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA, USA. (25) Center for Innate Immunity and Inflammation, Pelotonia Institute for Immuno-oncology, the James Comprehensive Cancer Center, Department of Surgery, Ohio State University, Columbus, OH, USA. (26) Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN, USA. (27) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. (28) Department of Medicine, Division of Rheumatic and Autoimmune Diseases, University of Minnesota, Minneapolis, MN, USA. (29) Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA. (30) Department of Microbiology and Immunology, Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30322, USA. (31) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: masopust@umn.edu.
