Perturbation of the natural killer cell compartment during primary human immunodeficiency virus 1 infection primarily involving the CD56^bright subset

Abstract

SummaryWe investigated the distribution of natural killer (NK) cell subsets, their activating and inhibitory receptors, and their cytolytic potential, in primary human immunodeficiency virus (HIV)-infected (PHI) individuals at baseline and during 1 year of follow-up with or without antiretroviral therapy, and compared the results with those obtained in treatment-naïve, chronically HIV-infected (CHI) individuals, and HIV-seronegative (HN) healthy individuals. The proportion of the CD56 dim and CD56 bright subsets decreased with disease progression, whereas that of the CD56 ) CD16 + subset increased. In the CD56 dim subset, the proportion of cells with natural cytotoxicity receptors (NCRs) decreased with disease progression, and their cytolytic potential was reduced. Conversely, the CD56 bright subset was characterized by a high proportion of NCR-positive, killer cell immunoglobulin-like receptor (KIR)-positive NKG2A + cells in both CHI and PHI individuals, which was associated with an increase in their cytolytic potential. During the 1 year of follow-up, the PHI individuals with high viraemia levels and low CD4 + T-cell counts who received highly active antiretroviral therapy (HAART) had a similar proportion of NK subsets to CHI individuals, while patients with low viraemia levels and high CD4 + T-cell counts who remained untreated had values similar to those of the HN individuals. Our results indicate a marked perturbation of the NK cell compartment during HIV-1 infection that is multifaceted, starts early and is progressive, primarily involves the CD56 bright subset, and is partially corrected by effective HAART.

Human CD56dimCD16dim Cells As an Individualized Natural Killer Cell Subset

“…As previously described, HIV-1 infection dramatically altered the distribution of NK cell subsets, with, respectively, reducing and increasing the percentages of CD56 dim and anergic CD56 − NK cells in viremic patients [Figure 2E; (30, 31)]. Both of these abnormalities were reverted by cART (32).…”

Effects of cryopreservation on effector cells for antibody dependent cell-mediated cytotoxicity (ADCC) and natural killer (NK) cell activity in 51Cr-release and CD107a assays

“…The CD16 low CD56 bright cells, are thought to be predominantly cytokines producers, are not usually thought to be cytotoxic (Cooper et al, 2001) and are more affected by HIV infection (Mantegani et al, 2009), had higher baseline expression of CD107a after freezing and thawing than the CD56 dim subset (data not shown). A new ADCC assay recently developed by (Helguera et al, 2011) may be useful in evaluating cytotoxic function for this NK subset since it would determine target lysis simultaneously to CD107a expression on the effectors.…”

Human CD56bright NK Cells: An Update

“…In primary HIV-infected patients, an increased expression of NKp46 (up to 100% of CD56 bright cells) is observed, whereas the opposite occurs in chronically infected subjects, in whom NKp46 expression on CD56 bright cells is even lower than in healthy donors (54,92). In primary infection, NKp46 expression could be indicative of an early stage postinfection.…”

“…In the case of virally infected cells, such as in HIV-infected individuals, progression of the disease is accompanied by a decreased frequency of CD56 bright NK cells (54).…”