PMID- 24842370 OWN - NLM STAT- MEDLINE DCOM- 20140820 LR - 20221109 IS - 1540-9538 (Electronic) IS - 0022-1007 (Print) IS - 0022-1007 (Linking) VI - 211 IP - 6 DP - 2014 Jun 2 TI - Lymph node stromal cells acquire peptide-MHCII complexes from dendritic cells and induce antigen-specific CD4(+) T cell tolerance. PG - 1153-66 LID - 10.1084/jem.20132000 [doi] AB - Dendritic cells (DCs), and more recently lymph node stromal cells (LNSCs), have been described to tolerize self-reactive CD8(+) T cells in LNs. Although LNSCs express MHCII, it is unknown whether they can also impact CD4(+) T cell functions. We show that the promoter IV (pIV) of class II transactivator (CIITA), the master regulator of MHCII expression, controls endogenous MHCII expression by LNSCs. Unexpectedly, LNSCs also acquire peptide-MHCII complexes from DCs and induce CD4(+) T cell dysfunction by presenting transferred complexes to naive CD4(+) T cells and preventing their proliferation and survival. Our data reveals a novel, alternative mechanism where LN-resident stromal cells tolerize CD4(+) T cells through the presentation of self-antigens via transferred peptide-MHCII complexes of DC origin. CI - (c) 2014 Dubrot et al. FAU - Dubrot, Juan AU - Dubrot J AD - Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland. FAU - Duraes, Fernanda V AU - Duraes FV AD - Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland. FAU - Potin, Lambert AU - Potin L AD - Laboratory of Lymphatic and Cancer Bioengineering, Institute of Bioengineering and Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. FAU - Capotosti, Francesca AU - Capotosti F AD - Laboratory of Lymphatic and Cancer Bioengineering, Institute of Bioengineering and Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland. FAU - Brighouse, Dale AU - Brighouse D AD - Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland. FAU - Suter, Tobias AU - Suter T AD - Department of Neurology, Section of Neuroimmunology and MS Research, University Hospital Zurich, 8091 Zurich, Switzerland. FAU - LeibundGut-Landmann, Salome AU - LeibundGut-Landmann S AD - Institute of Microbiology, Swiss Federal Institute of Technology Zurich, 8093 Zurich, Switzerland. FAU - Garbi, Natalio AU - Garbi N AD - Institute of Molecular Medicine and Institute of Experimental Immunology, University of Bonn, 53105 Bonn, Germany Institute of Molecular Medicine and Institute of Experimental Immunology, University of Bonn, 53105 Bonn, Germany. FAU - Reith, Walter AU - Reith W AD - Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland. FAU - Swartz, Melody A AU - Swartz MA AD - Laboratory of Lymphatic and Cancer Bioengineering, Institute of Bioengineering and Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland ISREC, SV, EPFL, 1015 Lausanne, Switzerland Stephanie.hugues@unige.ch melody.swartz@epfl.ch. FAU - Hugues, Stephanie AU - Hugues S AD - Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland Stephanie.hugues@unige.ch melody.swartz@epfl.ch. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140519 PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Antigens) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (MHC class II transactivator protein) RN - 0 (Nuclear Proteins) RN - 0 (Peptides) RN - 0 (Trans-Activators) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Antigen Presentation/immunology MH - Antigens/*immunology MH - CD4-Positive T-Lymphocytes/*immunology/metabolism MH - Cell Proliferation MH - Cells, Cultured MH - Dendritic Cells/*immunology/metabolism MH - Flow Cytometry MH - Gene Expression/drug effects/immunology MH - Histocompatibility Antigens Class II/genetics/immunology/metabolism MH - Immune Tolerance/*immunology MH - Interferon-gamma/immunology/pharmacology MH - Lymph Nodes/cytology/*immunology/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Nuclear Proteins/genetics/immunology/metabolism MH - Peptides/immunology/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Stromal Cells/*immunology/metabolism MH - Trans-Activators/genetics/immunology/metabolism PMC - PMC4042642 EDAT- 2014/05/21 06:00 MHDA- 2014/08/21 06:00 PMCR- 2014/12/02 CRDT- 2014/05/21 06:00 PHST- 2014/05/21 06:00 [entrez] PHST- 2014/05/21 06:00 [pubmed] PHST- 2014/08/21 06:00 [medline] PHST- 2014/12/02 00:00 [pmc-release] AID - jem.20132000 [pii] AID - 20132000 [pii] AID - 10.1084/jem.20132000 [doi] PST - ppublish SO - J Exp Med. 2014 Jun 2;211(6):1153-66. doi: 10.1084/jem.20132000. Epub 2014 May 19.