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The role of NK cells in HIV-1 protection: autologous, allogeneic or both?

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Show simple item record Hens, J. Jennes, W. Kestens, L. 2016-05-20T12:21:37Z 2016-05-20T12:21:37Z 2016
dc.identifier.issn 1742-6405
dc.identifier.other ITG-B1B
dc.identifier.other ITG-B2A
dc.identifier.other ITG-BLA
dc.identifier.other DBM
dc.identifier.other U-IMMUN
dc.identifier.other JIF
dc.identifier.other DOI
dc.identifier.other FTA
dc.identifier.other OAJ
dc.identifier.other Abstract
dc.identifier.other UPD62
dc.description.abstract Natural killer (NK) cells specialize in killing virally infected- or tumor cells and are part of the innate immune system. The activational state of NK cells is determined by the balance of incoming activating and inhibitory signals mediated by receptor-ligand binding with the target cell. These receptor-ligand bonds mainly consist of the killer immunoglobulin-like receptors (KIR), which are expressed at the cell surface of NK cells, and their ligands: the highly variable human leukocyte antigen -class I molecules (HLA). Absence of an inhibitory receptor-ligand bond lowers the NK cell activation threshold, whereas an activating receptor-ligand bond stimulates the cell, potentially overcoming this threshold and triggering NK cell activation. NK cells influence the course of infection as well as the acquisition of HIV-1. Several lines of evidence relate the activating NK cell receptor KIR3DS1, in the presence or absence of its putative ligand HLA-Bw4, with slower disease progression as well as resistance to HIV-1 infection. Overall, resistance to HIV-1 infection predominantly correlates with activating KIR/HLA profiles, consisting of e.g. activating KIRs, group B haplotypes, or inhibitory KIRs in absence of their ligands. Such a conclusion is less evident for studies of HIV-1 disease progression, with studies reporting beneficial as well as detrimental effects of activating KIR/HLA genotypes. It is likely that KIR/HLA association studies are complicated by the complexity of the KIR and HLA loci and their mutual interactions, as well as by additional factors like route of HIV exposure, immune activation, presence of co-infections, and the effect of anti-HIV-1 antibodies. One newly discovered NK cell activation pathway associated with resistance to HIV-1 infection involves the presence of an iKIR/HLA mismatch between partners. The absence of such an iKIR/HLA bond renders donor-derived allogeneic HIV-1 infected cells vulnerable to NK cell responses during HIV-1 transmission. Therefore, theoretically, HIV-1 would be eliminated before it has the chance to infect the autologous cells in the recipient. While this "alloreactive" NK cell mechanism is especially relevant to HIV transmission in monogamous couples, it would be interesting to investigate how it could influence resistance to HIV in other settings. The objective of this review is to summarize the knowledge about these autologous and alloreactive NK cell responses with regard to HIV-1 outcome. en_US
dc.language English en_US
dc.subject Viral diseases en_US
dc.subject HIV-1 en_US
dc.subject AIDS en_US
dc.subject Disease transmission, sexual en_US
dc.subject Immunity en_US
dc.subject Natural killer cells en_US
dc.subject Protection en_US
dc.subject KIR en_US
dc.subject HLA en_US
dc.subject Immunoglobulins en_US
dc.subject Immune activation en_US
dc.subject Autologous en_US
dc.subject Stem cell transplantation en_US
dc.subject Review of the literature en_US
dc.title The role of NK cells in HIV-1 protection: autologous, allogeneic or both? en_US
dc.type Article en_US
dc.citation.issue 15 en_US
dc.citation.jtitle AIDS Research and Therapy en_US
dc.citation.volume 13 en_US
dc.citation.pages 1-12 en_US
dc.citation.jabbreviation AIDS Res Ther en_US

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