Antibody dependent cellular cytotoxicity activity of effector cells from HIV infected Elite and Viral Controllers.

2016 | AIDS Res Hum Retroviruses

Abstract:

Carriage of alleles encoding certain inhibitory Natural Killer (NK) cell receptor/HLA ligand KIR3DL1/HLA-B combinations is associated with protection from HIV infection and slow time to AIDS, implicating NK cells in HIV control. NK cells also mediate antibody-dependent cellular cytotoxicity (ADCC). ADCC has been identified as a correlate of protection in secondary analyses of the modestly protective RV144 Thai HIV vaccine trial. In ADCC, HIV envelope (Env)-specific antibodies (Abs) bridge HIV infected or gp120 coated target cells and NK cells expressing CD16 receptors for Ab Fc domains. CD16 engagement activates NK cells to secrete cytokines/chemokines, degranulate, deliver granzyme B (GrB) to target cells and cytolysis. A subset of HIV+ subjects, known as Slow Progressors (SP), maintain low level viremia without treatment. HIV+ SPs versus progressors have higher titres and/or a greater breadth of ADCC competent Abs. Investigations of the functional capacity of NK effector cells following CD16 engagement in HIV+ subjects are lacking. We used the ADCC-GranToxiLux (ADCC-GTL) assay to assess the frequency of GrB+ (%GrB+) cells generated by effector cells from 37 HIV+ SP and 15 progressors to gp120 coated CEM.NKr.CCR5 target cells in the presence of anti-Env Abs. Subject groups were stratified according to whether or not they carried educating KIR3DL1/HLA-B combinations able to confer NK cells with functional potential. No differences were observed in %GrB+ target cells generated by effector cells from carriers of educating versus non-educating KIR3DL1/HLA-B pairs. The absence of an effect of NK cell education on this readout may be due to loss of the ability of educated NK cells from SPs to respond to Ab dependent stimulation and/or the lower frequency of KIR3DL1+ than KIR3DL1- NK cells that co-express CD16. That KIR/HLA genotypes have minimal impact on inter-individual differences in ADCC potency has relevance for therapeutic interventions that target ADCC for HIV control.

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Isitman G

BC Centre for Excellence in HIV/AIDS

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Antibody dependent cellular cytotoxicity activity of effector cells from HIV infected Elite and Viral Controllers.

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