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 transactiva...

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Authors: Dubrot-Armendáriz, J. (Juan)|||/items/b42afe78-7095-4682-8c2c-0904580d8d53, Duraes, F.V. (Fernanda V.)|||/items/3412a905-ce7e-4755-a84b-e50cba543d27, Potin, L. (Lambert)|||/items/135f861f-5edb-4f30-a66b-526950a559c2, Capotosti, F. (Francesca)|||/items/f72cb450-3002-40d1-9ca3-10b6110ce468, Brighouse, D. (Dale)|||/items/b526e470-5918-4ec1-9ef6-cc47fb647515, Suter, T. (Tobias)|||/items/0d5ded9f-5f1f-42ad-a5b8-abbd5681ffc4, LeibundGut-Landmann, S. (Salomé)|||/items/ab2f38f2-d14a-4af7-bd42-b1680e696323, Garbi, N. (Natalio)|||/items/d14ce3bd-802b-44fa-a62b-795275d75c80, Reith, W. (Walter)|||/items/ddc6cd9b-c893-4e92-ac21-46e826cefea7, Swartz, M.A. (Melody A.)|||/items/c4d26d07-77cd-4d33-a609-9963c16861a2, Hugues, S. (Stéphanie)|||/items/437178cd-54c9-41db-b5c9-fa25dea04152
Format: article
Publication Date:2014
Country:España
Institution:Universidad de Navarra
Repository:Dadun. Depósito Académico Digital de la Universidad de Navarra
Language:English
OAI Identifier:oai:dadun.unav.edu:10171/122595
Online Access:https://hdl.handle.net/10171/122595
Access Level:Open access
Keyword:Dendritic cells
Lymph node stromal cells
Major histocompatibility complex class II
Class II transactivator
CD4-positive T lymphocytes
Immune tolerance
Description
Summary: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.