Immune regulatory CNS-reactive CD8+ T cells in experimental autoimmune encephalomyelitis

Nathan R YORK; Jason P MENDOZA; Sterling B ORTEGA; Andrew BENAGH; Andrew F TYLER; Mihail FIRAN; Nitin J KARANDIKAR

doi:10.1016/j.jaut.2010.01.003

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Immune regulatory CNS-reactive CD8+ T cells in experimental autoimmune encephalomyelitis

Journal article

Open access

Peer reviewed

Immune regulatory CNS-reactive CD8+ T cells in experimental autoimmune encephalomyelitis

Nathan R YORK, Jason P MENDOZA, Sterling B ORTEGA, Andrew BENAGH, Andrew F TYLER, Mihail FIRAN and Nitin J KARANDIKAR

Journal of autoimmunity, Vol.35(1), pp.33-44

2010

DOI: 10.1016/j.jaut.2010.01.003

PMCID: PMC2878858

PMID: 20172692

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https://www.ncbi.nlm.nih.gov/pmc/articles/2878858View

Open Access

Abstract

Immune-based self-recognition and failure to modulate this response are believed to contribute to the debilitating autoimmune pathology observed in multiple sclerosis (MS). Studies from its murine model, experimental autoimmune encephalomyelitis (EAE), have shown that neuroantigen-specific CD4+T cells are capable of inducing disease, while their immune sibling, the CD8+T cells, have largely been ignored. To understand their role in autoimmune demyelination, we first confirmed that, similar to our observations in human MS, there is robust induction of neuroantigen-reactive CD8+T cells in several models, including MOG(35-55)/CFA-induced EAE. However, MOG(35-55)-specific CD8+T-cells, when purified, were unable to adoptively transfer disease into naïve mice (in contrast to CD4+T-cells). In fact, we observed that the transfer of these neuroantigen-specific CD8+T cells was able to suppress the induction of EAE and to inhibit ongoing EAE. These regulatory CD8+T cells produced IFN-gamma and perforin and were able to kill MOG loaded CD4+T-cells as well as CD4-depleted APC, suggesting a cytotoxic/suppressor mechanism. Inhibition of EAE was associated with both the modulation of APC function as well as decreased MOG-specific CD4+T cell responses. Our studies reveal a novel and unexpected immune regulatory function for neuroantigen-specific CD8+T cells and have interesting biologic and therapeutic implications.

Neurology

Fundamental and applied biological sciences. Psychology

Fundamental immunology

Biological and medical sciences

Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis

Medical sciences

Details

Title: Subtitle: Immune regulatory CNS-reactive CD8+ T cells in experimental autoimmune encephalomyelitis
Creators: Nathan R YORK - Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, United States
Jason P MENDOZA - Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, United States
Sterling B ORTEGA - Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, United States
Andrew BENAGH - Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, United States
Andrew F TYLER - Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, United States
Mihail FIRAN - Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, United States
Nitin J KARANDIKAR - Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, United States
Resource Type: Journal article
Publication Details: Journal of autoimmunity, Vol.35(1), pp.33-44
DOI: 10.1016/j.jaut.2010.01.003
PMID: 20172692
PMCID: PMC2878858
NLM abbreviation: J Autoimmun
ISSN: 0896-8411
eISSN: 1095-9157
Publisher: Elsevier; Kidlington
Language: English
Date published: 2010
Academic Unit: Pathology
Record Identifier: 9984047735202771

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