The overall goal of this proposal is to contribute to the understanding of how HIV-1 infected target cells influence NK cell phenotype, activation state, and viability. HIV-1 infected targets may influence NK cells in several ways; including HIV-1 envelope interactions with chemokine receptors expressed on activated NK cells and their relation to HIV-1 induced modulation of cytokine expression during HIV-1 disease. In the first aim, we propose to analyze NKs by incubating PBMCs with autologous CD4+ primary T cells infected with HIV-1 in vitro and testing for virus-induced modulation of NK activation state, viability, and proliferative capacity. We will evaluate NK activation by CD107a exposure upon target cell interaction and characterize proinflammatory and apoptosis related gene expression by RNase protection assays. In the second aim, we will investigate the accessory role of dendritic cells in NK recognition and killing of HIV-1 infected target cells, in order to test the general hypothesis that NK cells are impaired in their ability to lyse HIV-infected targets in the absence of accessory cell help. Overall, this research will improve our understanding of mechanisms of control of HIV and potentially identify new targets for intervention. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI068405-01
Application #
7060620
Study Section
AIDS Immunology and Pathogenesis Study Section (AIP)
Program Officer
Wassef, Nabila M
Project Start
2006-03-01
Project End
2008-02-29
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
1
Fiscal Year
2006
Total Cost
$45,976
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
075524595
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Tomescu, Costin; Tebas, Pablo; Montaner, Luis J (2017) IFN-? augments natural killer-mediated antibody-dependent cellular cytotoxicity of HIV-1-infected autologous CD4+ T cells regardless of major histocompatibility complex class 1 downregulation. AIDS 31:613-622
Tomescu, Costin; Tebas, Pablo; Montaner, Luis J (2017) IFN-? augments NK-mediated antibody-dependent cellular cytotoxicity (ADCC) of HIV-1 infected autologous CD4+ T cells regardless of MHC-I downregulation. AIDS :
Tomescu, Costin; Mavilio, Domenico; Montaner, Luis J (2015) Lysis of HIV-1-infected autologous CD4+ primary T cells by interferon-alpha-activated NK cells requires NKp46 and NKG2D. AIDS 29:1767-73
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Tomescu, Costin; Chehimi, Jihed; Maino, Vernon C et al. (2009) Retention of viability, cytotoxicity, and response to IL-2, IL-15, or IFN-alpha by human NK cells after CD107a degranulation. J Leukoc Biol 85:871-6
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Tomescu, Costin; Chehimi, Jihed; Maino, Vernon C et al. (2007) NK cell lysis of HIV-1-infected autologous CD4 primary T cells: requirement for IFN-mediated NK activation by plasmacytoid dendritic cells. J Immunol 179:2097-104