Using TCR transgenic mice, Boccasavia and Bovolenta et al. showed in vivo and in co-cultures that RhoG+/+ CD4+ T cells trogocytosed MHC-II/peptide (MHCp) and CD80/CD86 from antigen-loaded DCs and displayed MHCp to cognate naive T cells to induce proliferation. MHCp+ T cells and responding T cells were relatively enriched for Tregs and Th17 cells, respectively. In an Experimental Autoimmune Encephalomyelitis (EAE) model, trogocytosis-deficient RhoG-/- mice generated MOG-specific CD4+ T cells with reduced Th17/Treg ratios, and exhibited minimal EAE. Scarcity of antigen-presenting professional APCs favored T cell–T cell interaction and Th17 generation.
Contributed by Paula Hochman
ABSTRACT: T cells form immunological synapses with professional antigen-presenting cells (APCs) resulting in T cell activation and the acquisition of peptide antigen-MHC (pMHC) complexes from the plasma membrane of the APC. They thus become APCs themselves. We investigate the functional outcome of T-T cell antigen presentation by CD4 T cells and find that the antigen-presenting T cells (Tpres) predominantly differentiate into regulatory T cells (Treg), whereas T cells that have been stimulated by Tpres cells predominantly differentiate into Th17 pro-inflammatory cells. Using mice deficient in pMHC uptake by T cells, we show that T-T antigen presentation is important for the development of experimental autoimmune encephalitis and Th17 cell differentiation in vivo. By varying the professional APC:T cell ratio, we can modulate Treg versus Th17 differentiation in vitro and in vivo, suggesting that T-T antigen presentation underlies proinflammatory responses in conditions of antigen scarcity.
Author Info: (1) Interactions with the Environment Program, Centro Biologa Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientficas, Universidad Autnoma de Madrid, 28049 Madrid, S
Author Info: (1) Interactions with the Environment Program, Centro Biologa Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientficas, Universidad Autnoma de Madrid, 28049 Madrid, Spain. (2) Interactions with the Environment Program, Centro Biologa Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientficas, Universidad Autnoma de Madrid, 28049 Madrid, Spain. (3) Interactions with the Environment Program, Centro Biologa Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientficas, Universidad Autnoma de Madrid, 28049 Madrid, Spain. (4) Interactions with the Environment Program, Centro Biologa Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientficas, Universidad Autnoma de Madrid, 28049 Madrid, Spain. (5) Interactions with the Environment Program, Centro Biologa Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientficas, Universidad Autnoma de Madrid, 28049 Madrid, Spain. (6) Interactions with the Environment Program, Centro Biologa Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientficas, Universidad Autnoma de Madrid, 28049 Madrid, Spain. (7) Interactions with the Environment Program, Centro Biologa Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientficas, Universidad Autnoma de Madrid, 28049 Madrid, Spain. (8) Centro de Investigacin del Cncer, Instituto de Biologa Molecular y Celular del Cancer, and Centro de Investigacin Biomdica en Red de Cncer (CIBERONC), CSIC-University of Salamanca, Campus Unamuno s/n, 37007 Salamanca, Spain. (9) Center for Physiopathology Toulouse-Purpan, INSERM UMR1043/CNRS UMR5282, CHU Purpan, BP3028, 31024 Toulouse, France. (10) Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. (11) Interactions with the Environment Program, Centro Biologa Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientficas, Universidad Autnoma de Madrid, 28049 Madrid, Spain. Electronic address: balarcon@cbm.csic.es.
