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

Broadley, Iain, Pera, Alejandra, Morrow, George, Davies, Kevin and Kern, Florian (2017) 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. Frontiers in Immunology, 8. a195. ISSN 1664-3224

[img] PDF - Accepted Version
Available under License Creative Commons Attribution.

Download (4MB)
[img] PDF - Published Version
Available under License Creative Commons Attribution.

Download (1MB)

Abstract

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.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Brighton and Sussex Medical School > Neuroscience
Subjects: R Medicine
R Medicine > R Medicine (General)
R Medicine > R Medicine (General) > R852 Research. Experimentation
Depositing User: Sandy Gray
Date Deposited: 20 Feb 2017 09:47
Last Modified: 19 Aug 2017 18:12
URI: http://sro.sussex.ac.uk/id/eprint/66808

View download statistics for this item

📧 Request an update