Lymph node stromal cells acquire peptide-MHCII complexes from dendritic cells and induce antigen-specific CD4⁺ T cell tolerance.
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.
Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland.
Juan
J
Dubrot
Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland.
Fernanda V
FV
Duraes
Laboratory of Lymphatic and Cancer Bioengineering, Institute of Bioengineering and Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Lambert
L
Potin
Laboratory of Lymphatic and Cancer Bioengineering, Institute of Bioengineering and Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Francesca
F
Capotosti
Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland.
Dale
D
Brighouse
Department of Neurology, Section of Neuroimmunology and MS Research, University Hospital Zurich, 8091 Zurich, Switzerland.
Tobias
T
Suter
Institute of Microbiology, Swiss Federal Institute of Technology Zürich, 8093 Zurich, Switzerland.
Salomé
S
LeibundGut-Landmann
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.
Natalio
N
Garbi
Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland.
Walter
W
Reith
Laboratory of Lymphatic and Cancer Bioengineering, Institute of Bioengineering and Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland ISREC, SV, EPFL, 1015 Lausanne, Switzerland Stephanie.hugues@unige.ch melody.swartz@epfl.ch.
Melody A
MA
Swartz
Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland Stephanie.hugues@unige.ch melody.swartz@epfl.ch.
Stéphanie
S
Hugues
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000941:Antigens; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D010455:Peptides; D015534:Trans-Activators; D007371:Interferon-gamma