5th International AIDS Society Conference on HIV Pathogenesis and Treatment Cape Town - July 19 - 22, 2009

DIFFERENTIAL PLASMA TRAIL AND IFN-α LEVELS FOLLOWING THERAPY INTERRUPTION IN CHRONIC HIV-1 INFECTION: INABILITY OF PDC TO DIRECTLY LYSIS HIV-INFECTED AUTOLOGOUS CD4+ T CELLS

IAS Conf HIV Pathog Treat 2009 Jul 19-22;5th: Abstract No. MOAA202

J. Chehimi¹, E. Papasavvas¹, C. Tomescu¹, B. Gekonge¹, K. Vinekar², C. Carty³, A. Hancock¹, M. Pistilli¹, G. Reynolds¹, K. Mounzer⁴, J. Kostman³, L.J. Montaner ^1
1The Wistar Institute, Immunology, Philadelphia, United States, ²The University of Pennsylvania, Philadelphia, United States, ³The University of Pennsylvania, Infectious Diseases, Philadelphia, United States, ⁴Philadelphia Field Initiating Group for HIV-1 Trials (Philadelphia FIGHT), Philadelphia, United States

BACKGROUND: Plasmacytoid dendritic cells (PDC) have been implicated in AIDS pathogenesis through induction of IFN-α-TRAIL-DR5 induced apoptosis of CD4 T cells. We examined the relationship between HIV-induced activation of PDC, IFN-α (plasma and in vitro induced), TRAIL and CD4 T cell expression of DR5 expression following acute viremia at treatment interruption (TI), chronic viremia, or following in vitro mediated infection models.

METHODS: Fresh PBMC from consenting adult controls (N=31) and HIV+ subjects (N=69) was used. Plasma TRAIL and IFN-α were determined by ELISA. TRAIL in PDC, and DR5 in CD4 T cells were determined by FACS. Longitudinal analysis was done in 21 suppressed HIV+ subjects on ART undergoing TI. Lysis of infected SupT1 cells or purified primary autologous CD4 T cells infected in vitro, by same donor PDC or NK cells was determined by chromium release assay. Differences between groups were tested by Mann-Whitney and paired t tests.

RESULTS: Viremia resulting from TI showed a positive association with plasma TRAIL but not with IFN-α levels (comparable levels found in viremic, ART-treated and control subjects). Although TRAIL expression was increased in PDC of HIV+ compared to controls (p=0.0035), no significant changes in DR5 expression was seen in circulating CD4 T cells from patients compared to controls, or following in vitro infection/exposure to infectious or non-infectious virus or IFN-α. Following in vitro TLR7/9 activation, PDC did not lyse autologous primary HIV-infected CD4 cells, but did lyse infected CD4 cell lines SUP-T1 expressing DR5. PDC activation did increase NK cytotoxicity against infected targets.

CONCLUSIONS: We observe a lack of association between IFN-α, enhanced TRAIL and DR5 expression in circulating CD4 T cells in vivo. Importantly, our combined results findings suggest a predominant antiviral role for PDC if remaining functional rather than having a predominant role during viremia augmenting DR5-dependent CD4 T cell apoptosis.

Download PDF of this abstract.

Download Power Point Presentation.

2009-07-22
MOAA202
Oral Abstract Session: MOAA2 - Subversion of Immune Responses in HIV Infection

Copyright © 2009 - International AIDS Society (IAS). All information and content relating to the abstracts from the 5th International AIDS Society Conference on HIV Pathogenesis and Treatment, such as text, graphics, logos, button icons, images, audio clips, and software is protected by copyright. Permission is hereby granted for the non-commercial use or reproduction of the information on this web site, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from the Elton John AIDS Foundation, National Library of Medicine, AIDS Walk of Orange County, and donations from users like you. Always watch for outdated information. This article first appeared in 2009. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2009. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. Permission is hereby granted for the non-commercial use or reproduction of the information herein, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.