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 Rojas, Alejandra, Davies, Kevin A 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. p. 195. ISSN 1664-3224

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Abstract

A large proportion of cardiovascular (CV) 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 CVD, 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 CV mortality observed in these situations. The CD4+CD28- phenotype convincingly links CMV infection to CV mortality based on a direct cellular-pathological mechanism rather than epidemiological association.

Item Type: Article
Keywords: CD4 T cells; autoimmune diseases; cardiovascular diseases; chronic inflammatory disease; cytotoxic T cells
Schools and Departments: Brighton and Sussex Medical School > Clinical Medicine
Subjects: R Medicine
Depositing User: Jessica Stockdale
Date Deposited: 21 Apr 2017 14:35
Last Modified: 21 Apr 2017 14:41
URI: http://sro.sussex.ac.uk/id/eprint/67450

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