Expansion of the NKG2C+ Natural Killer–Cell Subset Is Associated With High-Risk Carotid Atherosclerotic Plaques in Seropositive Patients for Human Cytomegalovirus
Objective—Human cytomegalovirus (HCMV), a pathogen involved in the development and progression of atherosclerosis, promotes in some individuals a marked reconfiguration of the natural killer (NK)–cell compartment whose hallmark is a persistent expansion of a peripheral blood NK-cell subset expressing the CD94/NKG2C NK receptor. We aimed to evaluate whether the HCMV-associated NK-cell compartment reconfiguration is related to carotid atherosclerotic plaque (CAP) instability.
Approach and Results—NK receptor expression (ie, LILRB1, NKG2A, NKG2C, and killer immunoglobulin-like receptors) by peripheral NK and T cells was evaluated in 40 patients with HCMV+ with CAP, including nonatherosclerotic strokes (n=15) and healthy subjects (n=11) as controls. High-risk CAP (n=16), defined as carotid stenosis >50% with ipsilateral neurological symptomatology in the previous 180 days, compared with non–high-risk CAP had higher %NKG2C+ NK cells (29.5±22.4% versus 16.3±13.2%; P=0.026; odds ratio, 1.053; 95% confidence interval, 1.002–1.106; P=0.042), with a corresponding reduction in the NKG2A+ NK subset (31.7±17.8% versus 41.8±15.8%; P=0.072). The proportions of NKG2C+ NK cells in high-risk CAP were inversely correlated with the CD4+/CD8+ ratio (RSpearman=−0.629; P=0.009) and directly with high-sensitivity C-reactive protein levels (RPearson=0.591; P=0.012), consistent with higher subclinical systemic inflammation. The intraplaque inflammatory infiltrate, evaluated in 27 CAP obtained after endarterectomy, showed a higher presence of subintimal CD3+ lymphocytes in those patients with HCMV-induced changes in the peripheral NK- and T-cell compartments.
Conclusions—The expansion of NKG2C+ NK cells in patients with CAP seems to be associated with an increased risk of plaque destabilization in some patients with chronic HCMV infection.
- Received May 28, 2013.
- Accepted August 5, 2013.
- © 2013 American Heart Association, Inc.