Site-Specific DC Surface Signatures Influence CD4+ T Cell Co-stimulation and Lung-Homing

David Pejoski; Marie Ballester; Floriane Auderset; Maria Vono; Dennis Christensen; Peter Andersen; Paul Henri Lambert; Claire Anne Siegrist

doi:10.3389/fimmu.2019.01650

Site-Specific DC Surface Signatures Influence CD4⁺ T Cell Co-stimulation and Lung-Homing

David Pejoski^*, Marie Ballester, Floriane Auderset, Maria Vono, Dennis Christensen, Peter Andersen, Paul Henri Lambert, Claire Anne Siegrist

^*Corresponding author for this work

3 Citations (Scopus)

14 Downloads (Pure)

Abstract

Dendritic cells (DCs) that drain the gut and skin are known to favor the establishment of T cell populations that home to the original site of DC-antigen (Ag) encounter by providing soluble “imprinting” signals to T cells in the lymph node (LN). To study the induction of lung T cell-trafficking, we used a protein-adjuvant murine intranasal and intramuscular immunization model to compare in vivo-activated Ag⁺ DCs in the lung and muscle-draining LNs. Higher frequencies of Ag⁺ CD11b+ DCs were observed in lung-draining mediastinal LNs (MedLN) compared to muscle-draining inguinal LNs (ILN). Ag⁺ CD11b+ MedLN DCs were qualitatively superior at priming CD4+ T cells, which then expressed CD49a+ CXCR3+ and preferentially trafficked into the lung parenchyma. CD11b+ DCs from the MedLN expressed higher levels of surface podoplanin, Trem4, GL7, and the known co-stimulatory molecules CD80, CD86, and CD24. Blockade of specific MedLN DC molecules or the use of sorted DC and T cell co-cultures demonstrated that DC surface phenotype influences the ability to prime T cells that then home to the lung. Thus, the density of dLN Ag⁺ DCs, and DC surface molecule signatures are factors that can influence the output and differentiation of lung-homing CD4+ T cells.

Original language	English
Article number	1650
Journal	Frontiers in Immunology
Volume	10
Issue number	JULY
Number of pages	18
ISSN	1664-3224
DOIs	https://doi.org/10.3389/fimmu.2019.01650
Publication status	Published - 2019

Keywords

CD11b+ dendritic cells
Costimulation
Lung CD4+ T cells
Lung homing
Tissue imprinting
Vaccination route

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@article{64c15a046dfe4fdfa1a89ebb04f62000,

title = "Site-Specific DC Surface Signatures Influence CD4+ T Cell Co-stimulation and Lung-Homing",

abstract = "Dendritic cells (DCs) that drain the gut and skin are known to favor the establishment of T cell populations that home to the original site of DC-antigen (Ag) encounter by providing soluble “imprinting” signals to T cells in the lymph node (LN). To study the induction of lung T cell-trafficking, we used a protein-adjuvant murine intranasal and intramuscular immunization model to compare in vivo-activated Ag+ DCs in the lung and muscle-draining LNs. Higher frequencies of Ag+ CD11b+ DCs were observed in lung-draining mediastinal LNs (MedLN) compared to muscle-draining inguinal LNs (ILN). Ag+ CD11b+ MedLN DCs were qualitatively superior at priming CD4+ T cells, which then expressed CD49a+ CXCR3+ and preferentially trafficked into the lung parenchyma. CD11b+ DCs from the MedLN expressed higher levels of surface podoplanin, Trem4, GL7, and the known co-stimulatory molecules CD80, CD86, and CD24. Blockade of specific MedLN DC molecules or the use of sorted DC and T cell co-cultures demonstrated that DC surface phenotype influences the ability to prime T cells that then home to the lung. Thus, the density of dLN Ag+ DCs, and DC surface molecule signatures are factors that can influence the output and differentiation of lung-homing CD4+ T cells.",

keywords = "CD11b+ dendritic cells, Costimulation, Lung CD4+ T cells, Lung homing, Tissue imprinting, Vaccination route",

author = "David Pejoski and Marie Ballester and Floriane Auderset and Maria Vono and Dennis Christensen and Peter Andersen and Lambert, {Paul Henri} and Siegrist, {Claire Anne}",

year = "2019",

doi = "10.3389/fimmu.2019.01650",

language = "English",

volume = "10",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Research Foundation",

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T1 - Site-Specific DC Surface Signatures Influence CD4+ T Cell Co-stimulation and Lung-Homing

AU - Pejoski, David

AU - Ballester, Marie

AU - Auderset, Floriane

AU - Vono, Maria

AU - Christensen, Dennis

AU - Andersen, Peter

AU - Lambert, Paul Henri

AU - Siegrist, Claire Anne

PY - 2019

Y1 - 2019

N2 - Dendritic cells (DCs) that drain the gut and skin are known to favor the establishment of T cell populations that home to the original site of DC-antigen (Ag) encounter by providing soluble “imprinting” signals to T cells in the lymph node (LN). To study the induction of lung T cell-trafficking, we used a protein-adjuvant murine intranasal and intramuscular immunization model to compare in vivo-activated Ag+ DCs in the lung and muscle-draining LNs. Higher frequencies of Ag+ CD11b+ DCs were observed in lung-draining mediastinal LNs (MedLN) compared to muscle-draining inguinal LNs (ILN). Ag+ CD11b+ MedLN DCs were qualitatively superior at priming CD4+ T cells, which then expressed CD49a+ CXCR3+ and preferentially trafficked into the lung parenchyma. CD11b+ DCs from the MedLN expressed higher levels of surface podoplanin, Trem4, GL7, and the known co-stimulatory molecules CD80, CD86, and CD24. Blockade of specific MedLN DC molecules or the use of sorted DC and T cell co-cultures demonstrated that DC surface phenotype influences the ability to prime T cells that then home to the lung. Thus, the density of dLN Ag+ DCs, and DC surface molecule signatures are factors that can influence the output and differentiation of lung-homing CD4+ T cells.

AB - Dendritic cells (DCs) that drain the gut and skin are known to favor the establishment of T cell populations that home to the original site of DC-antigen (Ag) encounter by providing soluble “imprinting” signals to T cells in the lymph node (LN). To study the induction of lung T cell-trafficking, we used a protein-adjuvant murine intranasal and intramuscular immunization model to compare in vivo-activated Ag+ DCs in the lung and muscle-draining LNs. Higher frequencies of Ag+ CD11b+ DCs were observed in lung-draining mediastinal LNs (MedLN) compared to muscle-draining inguinal LNs (ILN). Ag+ CD11b+ MedLN DCs were qualitatively superior at priming CD4+ T cells, which then expressed CD49a+ CXCR3+ and preferentially trafficked into the lung parenchyma. CD11b+ DCs from the MedLN expressed higher levels of surface podoplanin, Trem4, GL7, and the known co-stimulatory molecules CD80, CD86, and CD24. Blockade of specific MedLN DC molecules or the use of sorted DC and T cell co-cultures demonstrated that DC surface phenotype influences the ability to prime T cells that then home to the lung. Thus, the density of dLN Ag+ DCs, and DC surface molecule signatures are factors that can influence the output and differentiation of lung-homing CD4+ T cells.

KW - CD11b+ dendritic cells

KW - Costimulation

KW - Lung CD4+ T cells

KW - Lung homing

KW - Tissue imprinting

KW - Vaccination route

U2 - 10.3389/fimmu.2019.01650

DO - 10.3389/fimmu.2019.01650

M3 - Journal article

C2 - 31396211

AN - SCOPUS:85069493984

SN - 1664-3224

VL - 10

JO - Frontiers in Immunology

JF - Frontiers in Immunology

IS - JULY

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ER -