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* HIV Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PA 19104;
Biological Research and Development, BD Biosciences, San Jose, CA, 95131;
Department of Biostatistics, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003;
Philadelphia Field Initiation Group for HIV Trials, Philadelphia, PA 19103; and
¶ Department of Infectious Diseases, University of Pennsylvania, Presbyterian Hospital, Philadelphia, PA 19104
We analyzed dendritic cell (DC) and NK cell compartments in relation to CD4 recovery in 21 HIV-infected subjects followed to <50 copies/ml once starting antiretroviral therapy (ART) and observed for 52 wk of sustained suppression. Although CD4 counts increased in all subjects in response to ART, we observed a restoration of functional plasmacytoid DC (PDC) after 52 wk of sustained suppression under ART (from 1850 cells/ml to 4550 cells/ml) to levels comparable to controls (5120 cells/ml) only in subjects with a low baseline viral load, which also rapidly suppressed to <50 copies/ml upon 
60 days from ART initiation. Recovery of PDC at week 52 correlates with level of CD95 expression on CD8 T cells and PDC frequency following first ART suppression. NK cytotoxic activity increased rapidly upon viral suppression (VS) and correlated with PDC function at week 52. However, restoration of total NK cells was incomplete even after 52 wk on ART (73 cells/µl vs 122 cells/µl in controls). Direct reconstitution experiments indicate that NK cytotoxic activity against virally infected target cells requires DC/NK cooperation, and can be recovered upon sustained VS and recovery of functional PDC (but not myeloid DC) from ART-suppressed subjects. Our data indicate that viremic HIV-infected subjects may have different levels of reconstitution of DC and NK-mediated function following ART, with subjects with lower initial viremia and the greatest reduction of baseline immune activation at VS achieving the greatest level of innate effector cell reconstitution.
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 AI 51225 (to L.J.M.), AI 0587780 (to J.C.), AI 068405 (to C.T.), the Philadelphia Foundation, and the Fund from the Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health.
2 A portion of this work has been presented at the Society for Natural Immunity (Kauai, HI, November 4–8, 2005) and the Conference on Retroviruses and Opportunistic Infections (Denver, CO, February 5–8, 2006).
3 J.C. and L.A. contributed equally to this work.
4 Address correspondence and reprint requests to Dr. Luis J. Montaner, The Wistar Institute, 3601 Spruce Street, Room 480, Philadelphia, PA 19130. E-mail address: montaner{at}wistar.org
5 Abbreviations used in this paper: VS, viral suppression; DC, dendritic cell; MDC, myeloid DC; PDC, plasmacytoid DC; VL, viral load; ART, antiretroviral therapy; BL, baseline; AUC, area under the curve.
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  A. Iannello, O. Debbeche, S. Samarani, and A. Ahmad Antiviral NK cell responses in HIV infection: II. viral strategies for evasion and lessons for immunotherapy and vaccination J. Leukoc. Biol., July 1, 2008; 84(1): 27 - 49. [Abstract] [Full Text] [PDF]
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