Abstract
Context: The functional activity of NK cells depends on the balance between the engagement of activating and inhibitory receptors on the cell surface with their ligands, which enables them to kill infected cells. Objectives: The aim of this study was to evaluate and compare expressions of selected activating and inhibitory receptors on stimulated NK cells in HIV-1 and HIV-2 infections. Methods: PBMCs were analysed for activating (NKp30, NKp44, NKp46) and inhibitory (CD158a, CD158b, p70) receptor expressions in 30 HIV-1, 30 HIV-2 and 30 HIV uninfected healthy control (HC) subjects by flow cytometry after stimulating with K562 cells. Results: There was an expression of other receptors following an already in vitro engagement of NK cells with K562 cells. Higher expression of the activating receptors, NKp44 (p = 0.029) and NKp46 (p = 0.032) on NK cells from HIV-2 compared to HIV-1 infected individuals but similar NKp30 expression (p = 0.980). The levels of expression of inhibitory receptor CD158a were similar between HIV-1 and HIV-2 infected subjects (p = 0.309) but there was significant up-regulation of inhibitory receptors p70 (p = 0.010) and CD158b (p = 0.05) in HIV-1 compared to HIV-2 subjects. Conclusion: Despite the in vitro engagement of NK cells with stimulating K562 cells, our data showed differential expressions of other selected activating and inhibitory receptors in HIV-1 and HIV-2 infected subjects.
Highlights
The mechanisms underlying the long-term non-progression observed in many subjects with HIV-2 infection are yet to be elucidated and could be attributed to viral factors [1], host immune factor and/or the ability of the viruses to induce an effective immune response [2]
We have shown that effector Natural Killer (NK) cells, which are one of the key components of the innate immune response, have enhanced function in asymptomatic HIV-2 compared to HIV-1 individuals [5]
We previously showed an increase in NK cell activity in asymptomatic HIV-2 infected compared to HIV-1 infected individuals when ex vivo NK cells were stimulated with K562 cells [5]
Summary
The mechanisms underlying the long-term non-progression observed in many subjects with HIV-2 infection are yet to be elucidated and could be attributed to viral factors [1], host immune factor and/or the ability of the viruses to induce an effective immune response [2]. We have shown that effector NK cells, which are one of the key components of the innate immune response, have enhanced function in asymptomatic HIV-2 compared to HIV-1 individuals [5] This may contribute to an effective immune response which results in prolonged stable CD4+ T cell counts and a healthy state. The inhibitory receptors are not engaged during down-regulation of MHC or altered MHC Class I expression as observed during HIV infection [7], permitting the activation of NK cells and subsequent lysis of their target cells. Such cytolysis is mediated through the perforin, granzyme B or Fas lytic pathway [8], or by antibody-dependent cell cytotoxicity through CD16 receptors expressed on NK cells [9]. Subsequent works have employed techniques that showed lysis of primary CD4 T cells by NK cells [12] [13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
