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The Education of NK Cells Determines Their Responsiveness to Autologous HIV-Infected CD4 T Cells

Abstract : Several studies support a role for specific killer immunoglobulin-like receptor (KIR)-HLA combinations in protection from HIV infection and slower progression to AIDS. Natural killer (NK) cells acquire effector functions through education, a process that requires the interaction of inhibitory NK cell receptors with their major histocompatibility complex (MHC) class I (or HLA class I [HLA-I]) ligands. HLA-C allo-types are ligands for the inhibitory KIRs (iKIRs) KIR2DL1, KIR2DL2, and KIR2DL3, whereas the ligand for KIR3DL1 is HLA-Bw4. HIV infection reduces the expression of HLA-A,-B, and-C on the surfaces of infected CD4 (iCD4) T cells. Here we investigated whether education through iKIR-HLA interactions influenced NK cell responses to autologous iCD4 cells. Enriched NK cells were stimulated with autologous iCD4 cells or with uninfected CD4 cells as controls. The capacities of single-positive (sp) KIR2DL1, KIR2DL2, KIR2DL3, and KIR3DL1 NK cells to produce CCL4, gamma inter-feron (IFN-␥), and/or CD107a were assessed by flow cytometry. Overall, we observed that the potency of NK cell education was directly related to the frequency of each spiKIR ϩ NK cell's ability to respond to the reduction of its cognate HLA ligand on autologous iCD4 cells, as measured by the frequency of production by spiKIR ϩ NK cells of CCL4, IFN-␥, and/or CD107a. Both NK cell education and HIV-mediated changes in HLA expression influenced NK cell responses to iCD4 cells.
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Submitted on : Friday, April 17, 2020 - 10:24:06 AM
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Zahra Kiani, Franck Dupuy, Julie Bruneau, Bertrand Lebouché, Christelle Retière, et al.. The Education of NK Cells Determines Their Responsiveness to Autologous HIV-Infected CD4 T Cells. Journal of Virology, American Society for Microbiology, 2019, 93 (23), pp.e01185-19. ⟨10.1128/JVI.01185-19⟩. ⟨inserm-02545475⟩

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