title: Low CD4+ T cell counts among African HIV-1 infected subjects with group B KIR haplotypes in the absence of specific inhibitory KIR ligands.
abstract: Natural killer (NK) cells are regulated by interactions between polymorphic killer immunoglobulin-like receptors (KIR) and human leukocyte antigens (HLA). Genotypic combinations of KIR3DS1/L1 and HLA Bw4-80I were previously shown to influence HIV-1 disease progression, however other KIR genes have not been well studied. In this study, we analyzed the influence of all activating and inhibitory KIR, in association with the known HLA inhibitory KIR ligands, on markers of disease progression in a West African population of therapy-naïve HIV-1 infected subjects. We observed a significant association between carriage of a group B KIR haplotype and lower CD4+ T cell counts, with an additional effect for KIR3DS1 within the frame of this haplotype. In contrast, we found that individuals carrying genes for the inhibitory KIR ligands HLA-Bw4 as well as HLA-C1 showed significantly higher CD4+ T cell counts. These associations were independent from the viral load and from individual HIV-1 protective HLA alleles. Our data suggest that group B KIR haplotypes and lack of specific inhibitory KIR ligand genes, genotypes considered to favor NK cell activation, are predictive of HIV-1 disease progression.
authors.affiliation: Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium. wjennes@itg.be
authors.forename: Wim
authors.initials: W
authors.lastname: Jennes
authors.forename: Sonja
authors.initials: S
authors.lastname: Verheyden
authors.forename: Christian
authors.initials: C
authors.lastname: Demanet
authors.forename: Joris
authors.initials: J
authors.lastname: Menten
authors.forename: Bea
authors.initials: B
authors.lastname: Vuylsteke
authors.forename: John N
authors.initials: JN
authors.lastname: Nkengasong
authors.forename: Luc
authors.initials: L
authors.lastname: Kestens
mesh_terms: D000328:Adult; D000349:Africa; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002452:Cell Count; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000472:pathogenicity*; D015235:HLA-B Antigens / Q000378:metabolism; D015236:HLA-C Antigens / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D008024:Ligands; D054340:Receptors, KIR / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D015236:HLA-C Antigens; D008024:Ligands; D054340:Receptors, KIR