Expansion of the NKG2C+ natural killer-cell subset is associated with high-risk carotid atherosclerotic plaques in seropositive patients for human cytomegalovirus

Autor: Angel Ois, Luis Roig, Elisa Cuadrado, Jaume Roquer, Francesc Alameda, Jose E Martínez-Rodríguez, Jessica Munné-Collado, Miguel López-Botet, Aura Muntasell, Teresa Baró, Raquel Rasal
Rok vydání: 2013
Předmět:
Zdroj: Arteriosclerosis, thrombosis, and vascular biology. 33(11)
ISSN: 1524-4636
Popis: 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 [KIR]) 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 ( R Spearman =−0.629; P =0.009) and directly with high-sensitivity C-reactive protein levels ( R Pearson =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.
Databáze: OpenAIRE