University of Sussex
Browse
fimmu-08-00195.pdf (1.76 MB)

Expansions of cytotoxic CD4+CD28- T-cells drive excess cardiovascular mortality in rheumatoid arthritis and other chronic inflammatory conditions and are triggered by CMV infection

Download (1.76 MB)
Version 2 2023-06-12, 08:38
Version 1 2023-06-09, 05:13
journal contribution
posted on 2023-06-12, 08:38 authored by Iain Broadley, Alejandra Pera RojasAlejandra Pera Rojas, George Morrow, Kevin DaviesKevin Davies, Florian KernFlorian Kern
A large proportion of cardiovascular pathology results from immune-mediated damage, including systemic inflammation and cellular proliferation, which cause a narrowing of the blood vessels. Expansions of cytotoxic CD4+ T-cells characterized by loss of CD28 (‘CD4+CD28- T-cells’ or ‘CD4+CD28null cells’) are closely associated with cardiovascular disease (CVD), in particular coronary artery damage. Direct involvement of these cells in damaging the vasculature has been demonstrated repeatedly. Moreover, CD4+CD28- T-cells are significantly increased in rheumatoid arthritis (RA) and other autoimmune conditions. It is striking that expansions of this subset beyond 1-2% occur exclusively in CMV-infected people. CMV infection itself is known to increase the severity of autoimmune diseases, in particular RA and has also been linked to increased vascular pathology. A review of the recent literature on immunological changes in cardiovascular disease, RA, and CMV infection provides strong evidence that expansions of cytotoxic CD4+CD28- T-cells in RA and other chronic inflammatory conditions are limited to CMV-infected patients and driven by CMV-infection. They are likely to be responsible for the excess cardiovascular mortality observed in these situations. The CD4+CD28- phenotype convincingly links CMV infection to cardiovascular mortality based on a direct cellular-pathological mechanism rather than epidemiological association.

History

Publication status

  • Published

File Version

  • Published version

Journal

Frontiers in Immunology

ISSN

1664-3224

Publisher

Frontiers Media

Volume

8

Article number

a195

Department affiliated with

  • BSMS Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2017-02-20

First Open Access (FOA) Date

2017-02-20

First Compliant Deposit (FCD) Date

2017-02-20

Usage metrics

    University of Sussex (Publications)

    Categories

    No categories selected

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC