Human immunodeficiency virus type 1 infection is associated with increased NK cell polyfunctionality and higher levels of KIR3DL1+ NK cells in ugandans carrying the HLA-B Bw4 motif

Natural killer (NK) cells are important innate effector cells controlled by an array of activating and inhibitory receptors. Some alleles of the inhibitory killer-cell immunoglobulin-like receptor KIR3DL1 in combination with its HLA class I ligand Bw4 have been genetically associated with slower HIV...

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Published in:Journal of virology Vol. 85; no. 10; p. 4802
Main Authors: Eller, Michael A, Koehler, Rebecca N, Kijak, Gustavo H, Eller, Leigh Anne, Guwatudde, David, Marovich, Mary A, Michael, Nelson L, de Souza, Mark S, Wabwire-Mangen, Fred, Robb, Merlin L, Currier, Jeffrey R, Sandberg, Johan K
Format: Journal Article
Language:English
Published: United States 01.05.2011
Subjects:
Adult
CD56 Antigen - analysis
HIV Infections - immunology
HIV-1 - immunology
HLA-B Antigens - analysis
Humans
Killer Cells, Natural - chemistry
Killer Cells, Natural - immunology
Lymphocyte Subsets - chemistry
Lymphocyte Subsets - immunology
Middle Aged
Receptors, KIR3DL1 - analysis
Uganda
Viral Load
ISSN:1098-5514, 1098-5514
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Summary:Natural killer (NK) cells are important innate effector cells controlled by an array of activating and inhibitory receptors. Some alleles of the inhibitory killer-cell immunoglobulin-like receptor KIR3DL1 in combination with its HLA class I ligand Bw4 have been genetically associated with slower HIV-1 disease progression. Here, we observed that the presence of HLA-B Bw4 was associated with elevated frequencies of KIR3DL1(+) CD56(dim) NK cells in chronically HIV-1-infected individuals from the rural district of Kayunga, Uganda. In contrast, levels of KIR2DL1(+) CD56(dim) NK cells were decreased, and levels of KIR2DL3(+) CD56(dim) NK cells were unchanged in infected subjects carrying their respective HLA-C ligands. Furthermore, the size of the KIR3DL1(+) NK cell subset correlated directly with viral load, and this effect occurred only in HLA-B Bw4(+) patients, suggesting that these cells expand in response to viral replication but may have relatively poor antiviral capacity. In contrast, no association with viral load was present for KIR2DL1(+) and KIR2DL3(+) NK cells. Interestingly, chronic HIV-1 infection was associated with an increased polyfunctional response in the NK cell compartment, and, upon further investigation, KIR3DL1(+) CD56(dim) NK cells exhibited a significantly increased functional response in the patients carrying HLA-B Bw4. These results indicate that chronic HIV-1 infection is associated with increased NK cell polyfunctionality and elevated levels of KIR3DL1(+) NK cells in Ugandans carrying the HLA-B Bw4 motif.
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ISSN:1098-5514
1098-5514
DOI:10.1128/JVI.00111-11