Low CD4+ T cell counts among African HIV-1 infected subjects with group B KIR haplotypes in the absence of specific inhibitory KIR ligands |
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Authors: | Jennes Wim Verheyden Sonja Demanet Christian Menten Joris Vuylsteke Bea Nkengasong John N Kestens Luc |
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Institution: | Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium. wjennes@itg.be |
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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. |
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