title: 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.
abstract: 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.
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden. meller@hivresearch.org
authors.forename: Michael A
authors.initials: MA
authors.lastname: Eller
authors.forename: Rebecca N
authors.initials: RN
authors.lastname: Koehler
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Kijak
authors.forename: Leigh Anne
authors.initials: LA
authors.lastname: Eller
authors.forename: David
authors.initials: D
authors.lastname: Guwatudde
authors.forename: Mary A
authors.initials: MA
authors.lastname: Marovich
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.forename: Mark S
authors.initials: MS
authors.lastname: de Souza
authors.forename: Fred
authors.initials: F
authors.lastname: Wabwire-Mangen
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Currier
authors.forename: Johan K
authors.initials: JK
authors.lastname: Sandberg
mesh_terms: D000328:Adult; D019002:CD56 Antigen / Q000032:analysis; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015235:HLA-B Antigens / Q000032:analysis*; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry* / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D008875:Middle Aged; D054341:Receptors, KIR3DL1 / Q000032:analysis*; D014454:Uganda; D019562:Viral Load
chemical_list: D019002:CD56 Antigen; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C515083:KIR3DL1 protein, human; C522918:NCAM1 protein, human; D054341:Receptors, KIR3DL1