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

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...

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Autores principales:	Farah R. Itani, Sushmita Sinha, Ashley A. Brate, Lecia L. Pewe, Katherine N. Gibson-Corley, John T. Harty, Nitin J. Karandikar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8eae2beb3d1a4d938264ac020cf5dcc2
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spelling	oai:doaj.org-article:8eae2beb3d1a4d938264ac020cf5dcc22021-12-02T15:05:35ZSuppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen10.1038/s41598-017-01771-82045-2322https://doaj.org/article/8eae2beb3d1a4d938264ac020cf5dcc22017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01771-8https://doaj.org/toc/2045-2322Abstract 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.Farah R. ItaniSushmita SinhaAshley A. BrateLecia L. PeweKatherine N. Gibson-CorleyJohn T. HartyNitin J. KarandikarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Farah R. Itani Sushmita Sinha Ashley A. Brate Lecia L. Pewe Katherine N. Gibson-Corley John T. Harty Nitin J. Karandikar Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen
description	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.
format	article
author	Farah R. Itani Sushmita Sinha Ashley A. Brate Lecia L. Pewe Katherine N. Gibson-Corley John T. Harty Nitin J. Karandikar
author_facet	Farah R. Itani Sushmita Sinha Ashley A. Brate Lecia L. Pewe Katherine N. Gibson-Corley John T. Harty Nitin J. Karandikar
author_sort	Farah R. Itani
title	Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen
title_short	Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen
title_full	Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen
title_fullStr	Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen
title_full_unstemmed	Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen
title_sort	suppression of autoimmune demyelinating disease by preferential stimulation of cns-specific cd8 t cells using listeria-encoded neuroantigen
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8eae2beb3d1a4d938264ac020cf5dcc2
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Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen

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