Broadley, IainPera, AlejandraMorrow, GeorgeDavies, Kevin AKern, Florian2025-01-072025-01-072017-03-021664-3224https://hdl.handle.net/10668/28289A 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/CD4 T cellsautoimmune diseasescardiovascular diseaseschronic inflammatory diseasecytotoxic T cellsresearch article28303136open access10.3389/fimmu.2017.00195PMC5332470https://www.frontiersin.org/articles/10.3389/fimmu.2017.00195/pdfhttps://pmc.ncbi.nlm.nih.gov/articles/PMC5332470/pdf