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Regulation of T-Cell Functions by Oxidative Stress

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Studies on Arthritis and Joint Disorders

Abstract

The principal role of adaptive immunity is to distinguish between “self” and “nonself” and thus provide a highly specific line of immunological defence for the efficient removal of foreign material. It comprises of two arms: the effector B-cell arm and effector T-cell arm which act together to remove nonself. The balance between oxidising and reducing agents within these immune cells governs their redox state. This is important as transient controlled changes in the redox state, such as increased production of reactive oxygen species, are vital for signalling and induction of various biological processes, including cell growth and apoptosis. However, in chronic inflammatory diseases, the prolonged and persistent production of ROS, which overwhelms cellular antioxidant systems leading to oxidative stress, may influence T-cell function. This contributes to a T-cell phenotype which is hyporesponsive to growth and death signals and persists at the site of inflammation, perpetuating the immune response. The regulation of T-cell function by oxidative stress therefore has implications for rheumatoid arthritis.

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Abbreviations

APC:

Antigen-presenting cell

DC:

Dendritic cell

DMARD:

Disease-modifying antirheumatic drug

GSH:

Reduced glutathione

GSSG:

Oxidised glutathione

H2O2 :

Hydrogen peroxide

iGSH:

Intracellular glutathione

IL-1b:

Interleukin-1β

IL-2:

Interleukin-2

LAT:

Linker for activation of T cells

MDA:

Malondialdehyde

MTX:

Methotrexate

NAC:

N-acetylcysteine

NFκB:

Nuclear factor kappa B

NO:

Nitric oxide

NOS:

Nitric oxide synthase

O2 •− :

Superoxide anion radical

ONOO:

Peroxynitrite

PBMC:

Peripheral blood mononuclear cells

RA:

Rheumatoid arthritis

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

TCR:

T-cell receptor

TNFα:

Tumour necrosis factor-α

Treg:

Regulatory T cell

Trx:

Thioredoxin

TXRX1:

Thioredoxin reductase 1

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Authors and Affiliations

  1. School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, West Midlands, UK

    Stuart J. Bennett & Helen R. Griffiths

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  1. Stuart J. Bennett
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  2. Helen R. Griffiths
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Correspondence to Helen R. Griffiths .

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Editors and Affiliations

  1. Fac Farmacia, Department of Pharmacology, University of Valencia, Av Vicent Andres Estelles S/n Burjasot, Valencia, 46100, Spain

    Maria Jose Alcaraz

  2. , NEIRID Lab, Santiago University Clinical Hospital, Trav. Choupana sn, Santiago de Compostela, 15706, Spain

    Oreste Gualillo

  3. Fundación Jiménez Díaz Hospital, Rheumatology Division, Autonoma University, Avda Reyes Católicos 2, Madrid, 28040, Spain

    Olga Sánchez-Pernaute

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Bennett, S.J., Griffiths, H.R. (2013). Regulation of T-Cell Functions by Oxidative Stress. In: Alcaraz, M., Gualillo, O., Sánchez-Pernaute, O. (eds) Studies on Arthritis and Joint Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-6166-1_2

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