Uncoupling activation-induced modulation of CD16 and CD69 in CD56+ cells during AIDS

The immune system of HIV+ patients is chronically activated, which has been associated with a detrimental effect on both innate and acquired immunity during AIDS. We analyzed the expression and modulation of the triggering markers CD69 and CD16 in CD56+ cells from 18 asymptomatic HIV+ individuals and 8 AIDS patients, compared with 21 seronegative subjects. We observed a diminished PMA-induced CD16 downregulation in AIDS patients (p<0.01), associated with low numbers of CD4+ cells (p<0.02). Furthermore, an enhanced unstimulated expression of CD69 in asymptomatic HIV+ patients (p<0.05) was shown. AIDS patients could not efficiently upregulate PHA-dependent CD69 expression (p<0.05), which correlated with low CD4+ counts (p< 0.05). These abnormalities in CD16 and CD69 modulation were recorded in patients under highly active antiretroviral therapy (HAART). Our results demonstrate an altered modulation of two functionally relevant receptors in CD56+ cells from AIDS patients, contributing to our understanding of the immunopathogeny of NK cell dysfunction during disease progression.