Lymphocyte activation as a possible measure of atherosclerotic risk in patients with sleep apnea

Obstructive sleep apnea (OSA), a breathing disorder in sleep characterized by intermittent hypoxia and sleep fragmentation, constitutes an independent risk factor for cardiovascular morbidity. Investigating how this breathing disorder modulates immune responses may facilitate understanding one of the risk factors for atherosclerosis. T cells play a significant role in atherogenesis and plaque development via cytokine production and by directly contributing to vascular injury. Using flow cytometry and chromium release assays, we found that CD4 and CD8 T cells of OSA patients undergo phenotypic and functional changes and acquire cytotoxic capabilities. Thus, a shift in CD4 and CD8 T cells toward type 2 cytokine dominance with increased IL-4 expression was noted. IL-10 expression in T cells was negatively correlated with the severity of OSA, as determined by the apnea-hypopnea index (AHI), whereas TNF-alpha was positively correlated. CD8 T cells of OSA patients expressed a fourfold increase in TNF-alpha and CD40 ligand (CD40L), and exhibited an increased OSA severity-dependent cytotoxicity against endothelial cells. The percentage of CD4(+)CD28(null) and cytotoxicity of CD4 T lymphocytes were also significantly higher in OSA patients than in controls. Nasal continuous positive airway pressure (nCPAP) treatment, which ameliorated the severity of OSA, significantly lowered TNF-alpha and CD40L expression, and decreased cytotoxicity in CD8 T cells. In conclusion, increased cytotoxicity and cytokine imbalance in CD4 and CD8 T cells may be involved in atherogenesis in OSA. Nasal CPAP treatment ameliorates some lymphocyte dysfunctions and thus may moderate some atherogenic pathways.