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
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 KernA 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 ImmunologyISSN
1664-3224Publisher
Frontiers MediaExternal DOI
Volume
8Article number
a195Department affiliated with
- BSMS Publications
Full text available
- Yes
Peer reviewed?
- Yes