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* Department of Infectious Diseases and Microbiology, Graduate School of Public Health,
Center for Vaccine Research,
Division of Laboratory Animal Resources, and
Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261
The loss of myeloid (mDC) and plasmacytoid dendritic cells (pDC) from the blood of HIV-infected individuals is associated with progressive disease. It has been proposed that DC loss is due to increased recruitment to lymph nodes, although this has not been directly tested. Similarly as in HIV-infected humans, we found that lineage-negative (Lin–) HLA-DR+CD11c+CD123– mDC and Lin–HLA-DR+CD11c–CD123+ pDC were lost from the blood of SIV-infected rhesus macaques with AIDS. In the peripheral lymph nodes of SIV-naive monkeys the majority of mDC were mature cells derived from skin that expressed high levels of HLA-DR, CD83, costimulatory molecules, and the Langerhans cell marker CD1a, whereas pDC expressed low levels of HLA-DR and CD40 and lacked costimulatory molecules, similar to pDC in blood. Surprisingly, both DC subsets were depleted from peripheral and mesenteric lymph nodes and spleens in monkeys with AIDS, although the activation status of the remaining DC subsets was similar to that of DC in health. In peripheral and mesenteric lymph nodes from animals with AIDS there was an accumulation of Lin–HLA-DRmoderateCD11c–CD123– cells that resembled monocytoid cells but failed to acquire a DC phenotype upon culture, suggesting they were not DC precursors. mDC and pDC from the lymphoid tissues of monkeys with AIDS were prone to spontaneous death in culture, indicating that apoptosis may be a mechanism for their loss in disease. These findings demonstrate that DC are lost from rather than recruited to lymphoid tissue in advanced SIV infection, suggesting that systemic DC depletion plays a direct role in the pathophysiology of AIDS.
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 National Institutes of Health Grants AI43664 and AI055794 (to S.M.B.B.) and AI065380 (to K.N.B.).
2 Address correspondence and reprint requests to Dr. Simon M. Barratt-Boyes, Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261. E-mail address: smbb{at}pitt.edu
3 Abbreviations used in this paper: DC, dendritic cell; mDC, myeloid DC; pDC, plasmacytoid DC; Lin, lineage; mod, moderate; rh, recombinant human.
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