Influence of Plasma Viremia on Defects in Number and Immunophenotype of Blood Dendritic Cell Subsets in Human Immunodeficiency Virus 1–Infected Individuals

Abstract

Dendritic cells (DCs) are postulated to be involved in transmission of human immunodeficiency virus (HIV) type 1 to T cells and in stimulation of HIV-1-specific cell-mediated immunity. Blood DCs have been categorized as myeloid (mDC) and plasmacytoid (pDC) subsets, on the basis of differences in phenotype and function. Blood DC subset numbers and expression of costimulatory molecules and HIV-1 coreceptors on DCs were measured in the blood of treated and untreated HIV-1-infected subjects and uninfected control subjects. Absolute numbers of mDCs and pDCs were lower in HIV-1-infected subjects than in control subjects, most significantly in those with active HIV-1 replication. Increased surface expression of costimulatory molecules was observed on both DC subsets in subjects with HIV-1 viremia. Highly active antiretroviral therapy suppression of plasma viremia resulted in increases in blood DC numbers and decreases in DC costimulatory molecule expression. These findings further define the impact of HIV-1 replication on blood DC subsets in vivo.

A six‐color flow cytometric assay for the analysis of peripheral blood dendritic cells

“…The lower constitutive expression of the costimulatory molecules CD80, CD86, and CD40 on pDCs than mDCs clearly documented with our assay is in accordance with the tolerogenic function ascribed to pDCs (16). A few observations of lower expression of these markers on pDCs have been previously reported, but with methods that used isolated or cultured PBDCs, or compared data obtained from different tubes (17)(18)(19)(20). In this respect, the direct comparison between DC subsets made possible by our 6-color assay may be more reliable.…”

Differential Restoration of Myeloid and Plasmacytoid Dendritic Cells in HIV-1-Infected Children after Treatment with Highly Active Antiretroviral Therapy

“…In concordance with studies conducted in adult populations (12)(13)(14)(15), both mDC percentages and their capability for IL-12 production were reduced in viremic children, indicating that this DC subset is also depleted in HIV-1 infection. Long-term HAART could suppress viral load and result in complete recovery of mDC frequency and function.…”

“…The significant positive correlation between pDC frequency and duration of HAART suggests that an extended period of antiviral therapy might be indicated to better restore circulating pDCs. It is noteworthy that recovery of pDCs was slower in our examined subjects than in adults in previous reports (15,35,36). This might be explained, in part, by differences in immune system plasticity between adults and children.…”

“…Although previous research has shown that HIV-1-infected individuals have reduced mDC and pDC levels (14,15,17,21), the characterization of blood DC subsets and their effect on immune reconstitution in HAART-treated HIV pediatric patients has not yet been well defined. In this report, we characterized blood DC subsets in HIV-1-infected children before and after treatment with HAART.…”

“…Based on phenotypic and functional characterizations, two distinct circulating DC subsets have been identified in humans, myeloid (mDCs) and plasmacytoid DCs (pDCs). Both populations were found to be impaired in HIV-1-infected patients (12)(13)(14)(15)(16)(17) and are susceptible to infection by both R5 and X4 HIV-1 isolates, although mDCs are more efficiently infected by R5 isolates (18,19). Along with CD4 T cell counts and decreased IFN-␣ production, pDC counts are considered to be independent predictors of clinical disease progression and the onset of opportunistic infections (12,13,16,17).…”