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LPS-treated bone marrow-derived dendritic cells induce immune tolerance through modulating differentiation of CD4+ regulatory T cell subpopulations mediated by 3G11 and CD127

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Abstract

Intravenous transfer of LPS-treated bone marrow-derived dendritic cells blocks development of autoimmunity induced by CD4+ T cells in vivo. However, cellular mechanisms of dendritic cell-mediated immune tolerance have not yet been fully elucidated. Here, we report that there are two new subpopulations of CD4+CD25+FoxP3+GITR+ regulatory T cells (CD127+3G11+ and CD127+3G11− cells). LPS-treated dendritic cells facilitate development of CD4+CD127+3G11− regulatory T cells but inhibit that of CD4+CD127+3G11+ regulatory T cells. LPS-induced tolerogenic dendritic cells may cause immune tolerance through modulating balance of different subsets of CD4+ regulatory T cells mediated by CD127 and 3G11. Our results imply a new potential cellular mechanism of dendritic cell-mediated immune tolerance.

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Abbreviations

APC:

Allophycocyanin

CD:

Cluster of differentiation

CFA:

Complete Freund’s adjuvant

DC:

Dendritic cell

EAE:

Experimental autoimmune encephalomyelitis

FCS:

Fetal calf serum

FITC:

Fluorescein isothiocyanate

FoxP3:

Forkhead/winged helix transcription factor

GITR:

Glucocorticoid-induced tumor necrosis factor receptor

IL:

Interleukin

IFN-γ:

Interferon gamma

i.p.:

Intraperitoneal

i.v.:

Intravenous

KLH:

Keyhole limpet hemocyanin

LPS:

Lipopolysaccharide

MOG:

Myelin oligodendrocyte glycoprotein

2-ME:

2-Mercaptoethanol

MS:

Multiple sclerosis

PBS:

Phosphate-buffered saline

pDCs:

Plasmacytoid dendritic cells

PE:

Phycoerythrin

PE-Cy7:

Phycoerythrin-cyanine 7

PerCP-Cy5.5:

Peridinin-chlorophylla-protein–cyanine 5.5 complexes

PT:

Pertussis toxin

s.c.:

Subcutaneous

SD:

Standard deviation

SEM:

Standard error of arithmetic mean

Th:

T helper cells

Treg :

Regulatory T cell

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Acknowledgements

We appreciate Mrs. Katherine Regan who carried out proofreading for this manuscript.

Author contributions

Dr. F. Zhou designed and conducted experiments. Dr. G.X. Zhang revised manuscript and Prof. A.M. Rostami supervised research.

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Authors and Affiliations

  1. Department of Neurology, Thomas Jefferson University, 900 Walnut Street, Philadelphia, PA, 19107, USA

    Fang Zhou, Guang-Xian Zhang & Abdolmohamad Rostami

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  1. Fang Zhou
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  2. Guang-Xian Zhang
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  3. Abdolmohamad Rostami
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Correspondence to Abdolmohamad Rostami.

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Zhou, F., Zhang, GX. & Rostami, A. LPS-treated bone marrow-derived dendritic cells induce immune tolerance through modulating differentiation of CD4+ regulatory T cell subpopulations mediated by 3G11 and CD127. Immunol Res 65, 630–638 (2017). https://doi.org/10.1007/s12026-016-8881-z

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