Neuroantigen-specific autoregulatory CD8+ T cells inhibit autoimmune demyelination through modulation of dendritic cell function

Venkatesh P Kashi; Sterling B Ortega; Nitin J Karandikar

doi:10.1371/journal.pone.0105763

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Neuroantigen-specific autoregulatory CD8+ T cells inhibit autoimmune demyelination through modulation of dendritic cell function

Journal article

Open access

Peer reviewed

Neuroantigen-specific autoregulatory CD8+ T cells inhibit autoimmune demyelination through modulation of dendritic cell function

Venkatesh P Kashi, Sterling B Ortega and Nitin J Karandikar

PloS one, Vol.9(8), pp.e105763-e105763

2014

DOI: 10.1371/journal.pone.0105763

PMCID: PMC4140828

PMID: 25144738

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Abstract

Experimental autoimmune encephalomyelitis (EAE) is a well-established murine model of multiple sclerosis, an immune-mediated demyelinating disorder of the central nervous system (CNS). We have previously shown that CNS-specific CD8+ T cells (CNS-CD8+) ameliorate EAE, at least in part through modulation of CNS-specific CD4+ T cell responses. In this study, we show that CNS-CD8+ also modulate the function of CD11c+ dendritic cells (DC), but not other APCs such as CD11b+ monocytes or B220+ B cells. DC from mice receiving either myelin oligodendrocyte glycoprotein-specific CD8+ (MOG-CD8+) or proteolipid protein-specific CD8+ (PLP-CD8+) T cells were rendered inefficient in priming T cell responses from naïve CD4+ T cells (OT-II) or supporting recall responses from CNS-specific CD4+ T cells. CNS-CD8+ did not alter DC subset distribution or MHC class II and CD86 expression, suggesting that DC maturation was not affected. However, the cytokine profile of DC from CNS-CD8+ recipients showed lower IL-12 and higher IL-10 production. These functions were not modulated in the absence of immunization with CD8-cognate antigen, suggesting an antigen-specific mechanism likely requiring CNS-CD8-DC interaction. Interestingly, blockade of IL-10 in vitro rescued CD4+ proliferation and in vivo expression of IL-10 was necessary for the suppression of EAE by MOG-CD8+. These studies demonstrate a complex interplay between CNS-specific CD8+ T cells, DC and pathogenic CD4+ T cells, with important implications for therapeutic interventions in this disease.

Myelin-Oligodendrocyte Glycoprotein - immunology

CD8-Positive T-Lymphocytes - pathology

Encephalomyelitis, Autoimmune, Experimental - pathology

Dendritic Cells - immunology

Dendritic Cells - pathology

Encephalomyelitis, Autoimmune, Experimental - immunology

CD4-Positive T-Lymphocytes - pathology

CD4-Positive T-Lymphocytes - immunology

Animals

Histocompatibility Antigens Class II - immunology

Autoantigens - immunology

Interleukin-12 - immunology

Multiple Sclerosis - immunology

Multiple Sclerosis - pathology

Female

Mice

B7-2 Antigen - immunology

CD8-Positive T-Lymphocytes - immunology

Interleukin-10 - immunology

Details

Title: Subtitle: Neuroantigen-specific autoregulatory CD8+ T cells inhibit autoimmune demyelination through modulation of dendritic cell function
Creators: Venkatesh P Kashi - Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
Sterling B Ortega - Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
Nitin J Karandikar - Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
Resource Type: Journal article
Publication Details: PloS one, Vol.9(8), pp.e105763-e105763
DOI: 10.1371/journal.pone.0105763
PMID: 25144738
PMCID: PMC4140828
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: K24 AI079272 / NIAID NIH HHS R01 AI092106 / NIAID NIH HHS R21 NS051837 / NINDS NIH HHS
Language: English
Date published: 2014
Academic Unit: Pathology
Record Identifier: 9984047678902771

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