AEGiS-AIDSWeekly: AIDS and HIV Therapy: Dendritic cell subsets drop even during successful antiretroviral therapy

Important note: Information in this article was accurate in June 2002. The state of the art may have changed since the publication date.

AIDS and HIV Therapy: Dendritic cell subsets drop even during successful antiretroviral therapy

AIDSWEEKLY Plus; June 17, 2002
Michael Greer, Senior Medical Writer

NewsRx -- Some dendritic cell (DC) subsets are depleted in HIV patients, even after otherwise successful antiretroviral therapy, researchers report.

"In humans, at least two distinct DC subsets have been characterized based on phenotypic markers: the myeloid DC (MDC) and the plasmacytoid DC (PDC)," explained Jihed Chehimi and colleagues working with the Wistar Institute in Philadelphia, the Children's Hospital of Philadelphia, the Philadelphia Field Initiation Group for HIV Trials, and Schering-Plough's Laboratory for Immunological Research in Dardilly, France.

Levels of PDCs fall sharply after HIV infection, and remain low even after effective viral suppression, Chehimi and coauthors found.

Significant (p<0.0001) loss of PDCs with the BDCA-2 (+) and Lin (-) HLA-DR (+) CD123 (+) phenotypes were seen in HIV patients compared with healthy controls, they said These irreversible reductions in PDC number were similar regardless of viral RNA levels or CD4 cell counts.

Unlike myeloid DCs, which produce interleukin (IL)-12, plasmacytoid DCs produce type I and II interferons. Accordingly, HIV patients demonstrated significant (p<0.0001) and persistent reductions in interferon-(alpha) production in response to infection, study data showed.

MDC cell counts did not drop significantly until viral loads rose above 5000 copies/mL (Persistent decreases in blood plasmacytoid dendritic cell number and function despite effective highly active antiretroviral therapy and increased blood myeloid dendritic cells in HIV-infected individuals, J Immunol 2002 May 1;168(9):4796-801.

"Our data suggest that DC subsets are differentially reconstituted during the immune recovery associated with antiviral therapy," Chehimi and colleagues concluded. "The persistent impairment of certain DC subsets may result in a sustained defect in DC-mediated innate immune functions despite an effective treatment regimen."

The corresponding author for this report is Luis J. Montaner, Wistar Institute, HIV Immunopathogenesis Laboratory, 3601 Spruce St., Room 480, Philadelphia, PA 19130, USA.

A search at www.NewsRx.net using the term "AIDS and HIV therapy" yielded 1146 articles in 28 specialized reports.

Key points reported in this study include:

The plasmacytoid dendritic cell (PDC) subset is profoundly and irreversibly reduced after HIV infection

PDC loss was similar regardless of viral load or CD4 cell count, and was accompanied by an equally sharp drop in viral-induced interferon-(alpha) production

Myeloid DC counts, by contrast, only dropped significantly at very high viral loads

This article was prepared by AIDS Weekly editors from staff and other reports.

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