RT Journal Article
T1 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.
A1 Broadley, Iain
A1 Pera, Alejandra
A1 Morrow, George
A1 Davies, Kevin A
A1 Kern, Florian
K1 CD4 T cells
K1 autoimmune diseases
K1 cardiovascular diseases
K1 chronic inflammatory disease
K1 cytotoxic T cells
AB 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.
SN 1664-3224
YR 2017
FD 2017-03-02
LK https://hdl.handle.net/10668/28289
UL https://hdl.handle.net/10668/28289
LA en
DS RISalud
RD Apr 4, 2025