Variations in Plasmacytoid Dendritic Cell (PDC) and Myeloid Dendritic Cell (MDC) Levels in HIV-Infected Subjects on and off Antiretroviral Therapy

DOI: 10.1007/s10875-006-8401-3Journal of Clinical Immunology, Vol. 26, No. 1, January 2006 ( C 2006)Variations in Plasmacytoid Dendritic Cell (PDC) and Myeloid

Dendritic Cell (MDC) Levels in HIV-Infected Subjectson and off Antiretroviral TherapyBARBARA SCHMIDT,1 SUE H. FUJIMURA,1 JEFFREY N. MARTIN,2 and JAY A. LEVY1,3Received: June 28, 2005; accepted: September 8, 2005Plasmacytoid and myeloid dendritic cells are reduced in AIDS

patients. The number of these circulating cells was assessed

cross-sectionally and longitudinally in 27 uninfected and 72

HIV-infected subjects on and off antiretroviral therapy. The plasmacytoid dendritic cell numbers were significantly reduced in

the HIV-infected subjects compared to controls (p< 0.001).

This reduction correlated directly with CD4+ cell counts (p<

0.001) and inversely with viral load (p< 0.001). These associations were found to a lesser degree for the myeloid dendritic

cells. Intra-assay variability of these dendritic cell counts was<10%. Antiretroviral therapy significantly increased plasmacytoid dendritic cell (p< 0.001) and CD4+ cell (p = 0.05)

counts at 8 months by 76.9% and 19%, respectively. The plasmacytoid dendritic cell levels responded more readily to viral load increases and decreases than CD4+ cells. Circulating

plasmacytoid dendritic cells may provide important additional

information about immune function in HIV-infected subjects

receiving or not receiving antiretroviral therapy.KEY WORDS: Plasmacytoid dendritic cells; myeloid dendritic cells;

HIV infection; CD4+ cells; antiretroviral therapy.INTRODUCTIONThere are two populations of dendritic cells in the blood,

the myeloid dendritic cells (MDC, pre-DC1) and lymphoid or plasmacytoid dendritic cells (PDC, pre-DC2)(1). Both cell populations are involved in the generation1Division Hematology/Oncology, Department of Medicine, University

of California, San Francisco, California.2Department of Epidemiology and Biostatistics, University of

California, San Francisco, California.3To whom correspondence should be addressed at Division of

Hematology/Oncology, Department of Medicine, University of

California School of Medicine, San Francisco, California 94143-1270;

e-mail: [email protected] innate and acquired immune responses by secretion

of type I interferons (IFN), TNF- (2, 3), and IL-12 (4,5). Following exposure to CD40 ligand, PDC mature into

dendritic cells that produce IL-4, IL-5, and IL-10, thus

promoting a type-2 immune reaction, whereas exposure

to viral pathogens drives a potent Th-1 response (6, 7).Accumulating evidence indicates both numerical and

functional deficiencies in the DC populations in HIV infection, suggesting their potentially important role in the

control of HIV replication. Reduced PDC and MDC numbers were reported in HIV primary infection...