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The Roles of Regulatory T Cells in Central Nervous System Autoimmunity

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Neuroimmune Diseases

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

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Abstract

Regulatory T (Treg) cells are a population of T cells that can functionally supress an immune response and are fundamental in maintaining T cell tolerance to self-antigens and immune homeostasis in the healthy individual. They exert strong suppressive functions through a variety of mechanisms, including modulation of antigen-presenting cell maturation or function, metabolic disruption, the production and secretion of anti-inflammatory cytokines and direct cytotoxicity. Treg cells are generally thought to have a beneficial role in most immune-mediated contexts, and a loss of suppressive capability and altered numbers in a variety of neurological conditions can occur. This review examines the role of Treg cells in the context of central nervous system (CNS) autoimmunity, and how they contribute to both relatively common and more rare diseases involving demyelination or degeneration of the CNS, including multiple sclerosis, neuromyelitis optica, acute disseminated encephalomyelitis, anti-NMDAR encephalitis, and narcolepsy with cataplexy. Although the role of Treg cells in some of these conditions is still very much in the preliminary stages, it is a feasible notion that with more research, harnessing the innate suppressive abilities of these potent immune cells will contribute to the development of novel therapeutics in autoimmune disorders of the CNS.

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Abbreviations

ADEM:

Acute disseminated encephalomyelitis

APCs:

Antigen-presenting cells

AQP4:

Aquaporin 4

A2AR:

Adenosine receptor 2A

BBB:

Blood–brain barrier

cAMP:

Cyclic adenosine monophosphate

CIS:

Clinically isolated syndrome

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

CTLA4:

Cytotoxic T lymphocyte antigen 4

DC:

Dendritic cell

DEREG:

DEpletion of REGulatory T cells

EAE:

Experimental autoimmune encephalomyelitis

Ebi3:

Epstein–Barr virus-induced gene 3

FoxP3:

Forkhead box protein 3

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

HLA:

Human leukocyte antigen

IBD:

Inflammatory bowel disease

IDO:

Indoleamine 2,3-dioxygenase

IFN:

Interferon

IgG:

Immunoglobulin G

IL:

Interleukin

iTreg:

Inducible regulatory T cell

LAG3:

Lymphocyte-activation gene 3

LH:

Lateral hypothalamus

MBP:

Myelin basic protein

MG:

Myasthenia gravis

MHV:

Mouse hepatitis virus

MOG:

Myelin oligodendrocyte glycoprotein

MS:

Multiple sclerosis

NMDAR:

N-methyl-D-aspartate receptor

NMO:

Neuromyelitis optica

NMOSD:

Neuromyelitis optica spectrum disorders

nTreg:

Natural regulatory T cell

NT1:

Narcolepsy type 1

PBMCs:

Peripheral blood mononuclear cells

PLP:

Proteolipoprotein

PPMS:

Primary progressive multiple sclerosis

RRMS:

Relapsing–remitting multiple sclerosis

SPMS:

Secondary progressive multiple sclerosis

TCRs:

T cell receptors

TGF:

Transforming growth factor

Th:

T helper cell

TNF:

Tumour necrosis factor

Treg:

Regulatory T cell

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  1. Neuropathic Pain Research Group, Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales (UNSW), Sydney, NSW, Australia

    Brooke A. Keating, Justin G. Lees & Gila Moalem-Taylor

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  1. Medical Education Promotion Center, Tokyo Medical University, Tokyo, Japan

    Hiroshi Mitoma

  2. Department of Neurology, CHU-Charleroi, Charleroi, Belgium, Department of Neurosciences, University of Mons, Mons, Belgium

    Mario Manto

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Keating, B.A., Lees, J.G., Moalem-Taylor, G. (2019). The Roles of Regulatory T Cells in Central Nervous System Autoimmunity. In: Mitoma, H., Manto, M. (eds) Neuroimmune Diseases. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-030-19515-1_6

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