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NK Cell Lysis of HIV-1-Infected Autologous CD4 Primary T Cells: Requirement for IFN-Mediated NK Activation by Plasmacytoid Dendritic Cells¹

Costin Tomescu^*, Jihed Chehimi^*, Vernon C. Maino and Luis J. Montaner^2,*

^* HIV Immunopathogenesis Laboratory, Wistar Institute, Philadelphia, PA 19104; and BD Biosciences, San Jose, CA 95131

In vivo, several mechanisms have been postulated to protect HIV-1-infected cells from NK surveillance. In vitro, previous research indicates HIV-1-infected autologous CD4⁺ primary T cells are resistant to NK lysis. We hypothesized that NK lysis of HIV-1-infected target cells would be augmented by the presence of accessory cells and/or accessory cell factors. In this study, we show that stimulation of plasmacytoid dendritic cells (PDC) with the TLR9 agonist, CpG ODN 2216, triggered NK lysis of HIV-1-infected autologous CD4⁺ primary T cells. PDC-stimulated NK lysis was dependent upon MHC class I (MHC-I) down-regulation on infected cells, and primary HIV-1 isolates that exhibited enhanced MHC-I down-regulation were more susceptible to NK-mediated lysis. PDC-stimulated NK lysis of HIV-1-infected autologous CD4⁺ primary T cells was blocked by neutralizing Abs to type 1 IFN and was perforin/granzyme dependent. Overall, our data suggest that HIV-infected cells are not innately resistant to NK lysis, and that exogenous NK stimulation derived from PDC can trigger NK cytotoxicity against HIV-1-infected autologous CD4⁺ primary T cells.

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 study was supported by grants from the National Institutes of Health (AI51225, AI47760, U01AI065279, AI07632, and AI068405), the Philadelphia Foundation, and funds from the Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health.

² Address correspondence and reprint requests to Dr. Luis J. Montaner, HIV Immunopathogenesis Laboratory, Wistar Institute, 3601 Spruce Street, Room 480, Philadelphia, PA 19104. E-mail address: Montaner{at}wistar.org

³ Abbreviations used in this paper: PDC, plasmacytoid dendritic cell; aHIV⁺CD4, autologous CD4⁺ primary T cells infected with HIV-1; ILT2, Ig-like transcript 2; KIR, killer Ig-related receptor; ODN, oligodeoxynucleotide.