Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen

Farah R Itani; Sushmita Sinha; Ashley A Brate; Lecia L Pewe; Katherine N Gibson-Corley; John T Harty; Nitin J Karandikar

doi:10.1038/s41598-017-01771-8

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Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen

Journal article

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Peer reviewed

Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen

Farah R Itani, Sushmita Sinha, Ashley A Brate, Lecia L Pewe, Katherine N Gibson-Corley, John T Harty and Nitin J Karandikar

Scientific reports, Vol.7(1), pp.1519-11

05/08/2017

DOI: 10.1038/s41598-017-01771-8

PMCID: PMC5431563

PMID: 28484224

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Abstract

CD8 T-cells predominate in CNS lesions of MS patients and display oligoclonal expansion. However, the role of myelin-specific CD8 T-cells in disease remains unclear, with studies showing protective and pathogenic roles in EAE. We demonstrated a disease-suppressive function for CNS-specific CD8 T-cells in a model where the antigen is exogenously administered in vivo and used for in vitro activation. To probe the nature of the CD8 response elicited by endogenously presented myelin antigens in vivo, we developed a novel approach utilizing infection with Listeria monocytogenes (LM) encoding proteolipid protein peptide (PLP) amino acids 178-191 (LM-PLP). LM-PLP infection preferentially induced PLP-specific CD8 T-cell responses. Despite the induction of PLP-specific CD8 T-cells, LM-PLP infection did not result in disease. In fact, LM-PLP infection resulted in significant amelioration of PLP178-191-induced EAE. Disease suppression was not observed in mice deficient in CD8 T-cells, IFN-γ or perforin. DTH responses and CNS infiltration were reduced in protected mice, and their CD4 T-cells had reduced capacity to induce tissue inflammation. Importantly, infection with LM-PLP ameliorated established disease. Our studies indicate that CD8 T-cells induced by endogenous presentation of PLP178-191 attenuate CNS autoimmunity in models of EAE, implicating the potential of this approach as a novel immunotherapeutic strategy.

Myelin Proteolipid Protein - immunology

Encephalomyelitis, Autoimmune, Experimental - pathology

Mice, Inbred C57BL

Central Nervous System - pathology

Encephalomyelitis, Autoimmune, Experimental - immunology

Organ Specificity

Listeria - metabolism

Mice, Knockout

Lymphocyte Activation - immunology

Animals

CD8-Positive T-Lymphocytes - immunology

Antigens, Bacterial - metabolism

Immunity, Cellular

Details

Title: Subtitle: Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen
Creators: Farah R Itani - Interdisciplinary Graduate Program in Immunology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
Sushmita Sinha - Department of Pathology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
Ashley A Brate - Interdisciplinary Graduate Program in Immunology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
Lecia L Pewe - Department of Microbiology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
Katherine N Gibson-Corley - Department of Pathology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
John T Harty - Interdisciplinary Graduate Program in Immunology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA
Nitin J Karandikar - Interdisciplinary Graduate Program in Immunology, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA. nitin-karandikar@uiowa.edu
Resource Type: Journal article
Publication Details: Scientific reports, Vol.7(1), pp.1519-11
DOI: 10.1038/s41598-017-01771-8
PMID: 28484224
PMCID: PMC5431563
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: England
Grant note: R01 AI042767 / NIAID NIH HHS R37 AI042767 / NIAID NIH HHS R21 AI042767 / NIAID NIH HHS R01 AI092106 / NIAID NIH HHS K24 AI079272 / NIAID NIH HHS T32 AI007485 / NIAID NIH HHS
Language: English
Date published: 05/08/2017
Academic Unit: Pathology; Ophthalmology and Visual Sciences
Record Identifier: 9984047623002771

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