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

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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 > Clinical and Experimental Medicine 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:	13 Aug 2019 09:06
URI:	http://sro.sussex.ac.uk/id/eprint/66808

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