HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sachdeva, N. Articles by Asthana, D. Search for Related Content PubMed PubMed Citation Articles by Sachdeva, N. Articles by Asthana, D.

Impaired Restoration of Plasmacytoid Dendritic Cells in HIV-1-Infected Patients with Poor CD4 T Cell Reconstitution Is Associated with Decrease in Capacity to Produce IFN- but Not Proinflammatory Cytokines¹

Naresh Sachdeva^*, Vishwaratn Asthana^*, Toye H. Brewer, Deborah Garcia and Deshratn Asthana^2,*

^* Laboratory for Clinical and Biological Studies, University of Miami-Miller School of Medicine, Miami, FL 33136; Project Outreach, University of Miami, Florida City, FL 33034; and Borinquen Health Care Center, Miami, FL 33137

We analyzed reconstitution characteristics of plasmacytoid dendritic cells (PDCs) and myeloid DCs-1 in 38 HIV-1-infected patients with impaired restoration of CD4 T cell counts despite prolonged suppression of plasma viremia (discordant) and compared them with 42 patients showing good immunological and virological responses following highly active antiretroviral therapy (HAART). While myeloid DCs showed spontaneous recovery following HAART in both the groups, the discordant patients demonstrated poor peripheral reconstitution of PDCs as compared with concordant patients. The ability of PDCs to produce IFN- following stimulation with TLR7 ligand imiquimod and TLR9 ligand CpG ODN-2216 was also impaired in discordant patients even after 2 years following initiation of HAART. Lower IFN- expression in the PDCs following TLR stimulation was further associated with lower expression of transcription factor, IFN regulatory factor-7. In contrast, production of TNF- and IL-6 following TLR stimulation was comparable in both groups of patients, indicating that impaired reconstitution characteristics do not affect the capacity of PDCs to produce proinflammatory cytokines. The discordant patients had significantly lower baseline CD4 T cell counts and higher baseline viral load at the initiation of HAART implying that lower baseline CD4 T cell counts and higher plasma viral load are associated with impaired restoration of CD4 T cells and PDCs, thus, increasing the susceptibility of discordant patients toward opportunistic infections despite virological control.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the University of Miami-Laboratory for Clinical and Biological Studies educational and training funds.

² Address correspondence and reprint requests to Dr. Deshratn Asthana, Laboratory for Clinical and Biological Studies, University of Miami-Miller School of Medicine, 1550 Northwest 10th Avenue, Fox Building, Suite 118, Miami, FL 33136. E-mail address: desh{at}miami.edu

³ Abbreviations used in this paper: HAART, highly active antiretroviral therapy; DC, dendritic cell; PDC, plasmacytoid DC; IRF, IFN regulatory factor; MDC, myeloid DC.