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Lymph node stromal cells acquire peptide–MHCII complexes from dendritic cells and induce antigen-specific CD4+T cell tolerance


Dubrot, Juan; Duraes, Fernanda V; Potin, Lambert; Capotosti, Francesca; Brighouse, Dale; Suter, Tobias; LeibundGut-Landmann, Salomé; Garbi, Natalio; Reith, Walter; Swartz, Melody A; Hugues, Stéphanie (2014). Lymph node stromal cells acquire peptide–MHCII complexes from dendritic cells and induce antigen-specific CD4+T cell tolerance. Journal of Experimental Medicine, 211(6):1153-1166.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Virology
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Language:English
Date:2 June 2014
Deposited On:26 Jun 2019 09:29
Last Modified:31 Jul 2020 03:27
Publisher:Rockefeller University Press
ISSN:0022-1007
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1084/jem.20132000
PubMed ID:24842370

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