Identification of natural killer cell receptor phenotypes associated with leukemia.
ABSTRACT Natural killer (NK) cells play a key role in defense against tumor cells that have the capacity to downregulate human leukocyte antigen (HLA) class I expression. It has been reported that leukemic cells can have downregulated expression of HLA class I molecules. The polymorphic nature of NK cell receptor (NKR) genes generates diverse repertoires in the human population, which display specificity in the innate immune response. In the present study, 11 KIR and two CD94/NKG2 receptors were genotyped by PCR-SSP in 96 leukemic patients and 148 healthy Caucasians. Here, we report a significant increased frequency of the more inhibitory AB killer cell immunoglobulin-like receptor (KIR) phenotype in leukemic patients compared to the controls (31.1% in healthy controls vs 51.0% in leukemic patients, Pc=0.002), which is related to the high prevalence of the inhibitory KIR2DL2 in this population (Pc=0.007). Moreover, two specific KIR phenotypes AB1 and AB9, including all inhibitory KIRs, were significantly associated with leukemic patients. Our study suggests that an important percentage of leukemic patients express a KIR phenotype in favor of escape from NK cell immunity.
Article: Differential association of gene content polymorphisms of killer cell immunoglobulin-like receptors with placental malaria in HIV- and HIV+ mothers.[show abstract] [hide abstract]
ABSTRACT: Pregnant women have abundant natural killer (NK) cells in their placenta, and NK cell function is regulated by polymorphisms of killer cell immunoglobulin-like receptors (KIRs). Previous studies report different roles of NK cells in the immune responses to placental malaria (PM) and human immunodeficiency virus (HIV-1) infections. Given these references, the aim of this study was to determine the association between KIR gene content polymorphism and PM infection in pregnant women of known HIV-1 status. Sixteen genes in the KIR family were analyzed in 688 pregnant Kenyan women. Gene content polymorphisms were assessed in relation to PM in HIV-1 negative and HIV-1 positive women, respectively. Results showed that in HIV-1 negative women, the presence of the individual genes KIR2DL1 and KIR2DL3 increased the odds of having PM, and the KIR2DL2/KIR2DL2 homozygotes were associated with protection from PM. However, the reverse relationship was observed in HIV-1 positive women, where the presence of individual KIR2DL3 was associated with protection from PM, and KIR2DL2/KIR2DL2 homozygotes increased the odds for susceptibility to PM. Further analysis of the HIV-1 positive women stratified by CD4 counts showed that this reverse association between KIR genes and PM remained only in the individuals with high CD4 cell counts but not in those with low CD4 cell counts. Collectively, these results suggest that inhibitory KIR2DL2 and KIR2DL3, which are alleles of the same locus, play a role in the inverse effects on PM and PM/HIV co-infection and the effect of KIR genes on PM in HIV positive women is dependent on high CD4 cell counts. In addition, analysis of linkage disequilibrium (LD) of the PM relevant KIR genes showed strong LD in women without PM regardless of their HIV status while LD was broken in those with PM, indicating possible selection pressure by malaria infection on the KIR genes.PLoS ONE 01/2012; 7(6):e38617. · 4.09 Impact Factor
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ABSTRACT: The antileukemic potential of natural killer (NK) cells has been of rising interest in recent years. Interactions between inhibitory killer cell immunoglobulin-like receptors (KIR) and HLA class I ligands seem to be critically involved in the immunosurveillance process. It is also well established that mismatching of HLA class I-encoded KIR ligands in the setting of hematopoietic stem cell transplantation leads to allorecognition of leukemic cells by NK cells, which is in line with the concept of missing-self recognition. Recent data now suggest that KIR gene polymorphism constitutes another important parameter that needs to be taken into account for selection of suitable stem cell donors. Moreover, the role of KIR gene polymorphism for predisposition to leukemia is a current matter of debate. Here, we would like to review the role of KIR function and genetic polymorphism for recognition of leukemia and discuss the impact of these findings for developing novel concepts for NK cell-based immunotherapy strategies.Frontiers in immunology. 01/2013; 4:27.
Article: Low CD4+ T cell counts among African HIV-1 infected subjects with group B KIR haplotypes in the absence of specific inhibitory KIR ligands.[show abstract] [hide abstract]
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.PLoS ONE 01/2011; 6(2):e17043. · 4.09 Impact Factor