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Defective CD8+CD28?regulatory T cell suppressor function in rheumatoid arthritis is restored by tumour necrosis factor inhibitor therapy

Ceeraz, S., Hall, C., Choy, Ernest Ho Sing, Spencer, J. and Corrigall, V. 2013. Defective CD8+CD28?regulatory T cell suppressor function in rheumatoid arthritis is restored by tumour necrosis factor inhibitor therapy. Clinical and Experimental Immunology 174 (1) , pp. 18-26. 10.1111/cei.12161

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Abstract

Summary: Balanced immunoregulatory networks are essential for maintenance of systemic tolerance. Disturbances in the homeostatic equilibrium between inflammatory mediators, immune regulators and immune effector cells are implicated directly in the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). In this study we characterize the peripheral blood CD8+CD28- regulatory T cells (Treg) contribution to the immunoregulatory network in health and in RA. In health, CD8+CD28- Treg are suppressive but, unlike CD4+Treg, they function predominantly through the action of soluble mediators such as interleukin (IL)-10 and transforming growth factor (TGF)-β. Neutralization of TGF-β consistently reduced CD8+CD28- Treg suppressor function in vitro. RA, CD8+CD28- Treg are increased numerically, but have reduced expression of inducible co-stimulator (ICOS) and programmed death 1 (PD-1) compared to healthy or disease controls. They produce more IL-10 but autologous T cells express less IL-10R. This expression was found to be restored following in-vitro addition of a tumour necrosis factor inhibitor (TNFi). Deficiencies in both the CD8+CD28- Treg population and reduced sensitivity of the T responder cells impact upon their regulatory function in RA. TNFi therapy partially restores CD8+CD28- Treg ability in vivo and in vitro, despite the defects in expression of functionally relevant molecules by RA CD8+CD28- Treg compared to healthy controls. This study places CD8+CD28- Treg cells in the scheme of immune regulation alongside CD4+ Treg cells, and highlights the importance of understanding impaired responsiveness to regulation that is common to these suppressor subsets and their restored function in response to TNFi therapy.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
R Medicine > RZ Other systems of medicine
Uncontrolled Keywords: Adult; Aged; Antigens, CD28; Antigens, CD8; Cell Culture Techniques; Coculture Techniques; Female; Humans; Immune Tolerance; Immunophenotyping; Male; Methotrexate; Middle Aged; T-Lymphocytes, Regulatory; Tumor Necrosis Factor-alpha
Publisher: Wiley-Blackwell
ISSN: 0009-9104
Last Modified: 04 Jun 2017 08:22
URI: http://orca.cf.ac.uk/id/eprint/76613

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