Calzada-Fraile et al. showed that the formation of antigen-induced DC/CD4+ T cell synapses “licensed” post-synaptic DCs (psDC) by upregulation of MHC-I proteins, the ER phagosome pathway of cross-presentation, and ER-associated protein degradation molecules, and increased lipid accumulation and peroxidation, which allowed endosomal antigen escape. psDC cross-presentation enhanced effector and naive CD8+ T cell activation. Adoptive transfer of psDCs protected mice from pathogenic infection by promoting specific effector and memory CD8+ T cell responses. psDC depletion during antigen/alum immunization of mice disabled antigen-specific CD8+ T cell response generation.
Contributed by Paula Hochman
ABSTRACT: Antigen cognate dendritic cell (DC)-T cell synaptic interactions drive activation of T cells and instruct DCs. Upon receiving CD4(+) T cell help, post-synaptic DCs (psDCs) are licensed to generate CD8(+) T cell responses. However, the cellular and molecular mechanisms that enable psDCs licensing remain unclear. Here, we describe that antigen presentation induces an upregulation of MHC-I protein molecules and increased lipid peroxidation on psDCs in vitro and in vivo. We also show that these events mediate DC licensing. In addition, psDC adoptive transfer enhances pathogen-specific CD8(+) T responses and protects mice from infection in a CD8(+) T cell-dependent manner. Conversely, depletion of psDCs in vivo abrogates antigen-specific CD8(+) T cell responses during immunization. Together, our data show that psDCs enable CD8(+) T cell responses in vivo during vaccination and reveal crucial molecular events underlying psDC licensing.
Author Info: (1) Centro Nacional de Investigaciones Cardiovasculares, 28029, Madrid, Spain. (2) Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense de M
Author Info: (1) Centro Nacional de Investigaciones Cardiovasculares, 28029, Madrid, Spain. (2) Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense de Madrid, 28040, Madrid, Spain. (3) Centro Nacional de Investigaciones Cardiovasculares, 28029, Madrid, Spain. (4) Centro Nacional de Investigaciones Cardiovasculares, 28029, Madrid, Spain. Centro de Investigacin Biomdica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029, Madrid, Spain. (5) Laboratory of Synthetic Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy. (6) Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense de Madrid, 28040, Madrid, Spain. (7) Centro de Investigacin Biomdica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029, Madrid, Spain. Dynamic Video Microscopy Unit, Immunology Department, Instituto de Investigacin Sanitaria Hospital Universitario La Princesa, Universidad Autnoma de Madrid, 28006, Madrid, Spain. (8) Microbiology Section, Departamento CC, Farmacuticas y de la Salud, Facultad de Farmacia, Universidad CEU San Pablo, Boadilla del Monte, 28668, Madrid, Spain. (9) Department of Molecular & Cellular Biology, Centro Nacional de Biotecnologa (CNB-CSIC), Madrid, Spain. (10) Centro Nacional de Investigaciones Cardiovasculares, 28029, Madrid, Spain. Centro de Investigacin Biomdica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029, Madrid, Spain. (11) Laboratory of Synthetic Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy. Veneto Institute of Oncology IOV-IRCCS, Padua, Italy. (12) Centro Nacional de Investigaciones Cardiovasculares, 28029, Madrid, Spain. fsmadrid@salud.madrid.org. Centro de Investigacin Biomdica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029, Madrid, Spain. fsmadrid@salud.madrid.org. Immunology Department, Instituto de Investigacin Sanitaria Hospital Universitario La Princesa, Universidad Autnoma de Madrid, 28006, Madrid, Spain. fsmadrid@salud.madrid.org.
