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CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes.

ABSTRACT: Antibody-dependent cellular cytotoxicity (ADCC) is exerted by immune cells expressing surface Fc? receptors (Fc?Rs) against cells coated with antibody, such as virus-infected or transformed cells. CD16, the Fc?RIIIA, is essential for ADCC by NK cells, and is also expressed by a subset of human blood monocytes. We found that human CD16- expressing monocytes have a broad spectrum of ADCC capacities and can kill cancer cell lines, primary leukemic cells and hepatitis B virus-infected cells in the presence of specific antibodies. Engagement of CD16 on monocytes by antibody bound to target cells activated ?2-integrins and induced TNF? secretion. In turn, this induced TNFR expression on the target cells, making them susceptible to TNF?-mediated cell death. Treatment with TLR agonists, DAMPs or cytokines, such as IFN?, further enhanced ADCC. Monocytes lacking CD16 did not exert ADCC but acquired this property after CD16 expression was induced by either cytokine stimulation or transient transfection. Notably, CD16+ monocytes from patients with leukemia also exerted potent ADCC. Hence, CD16+ monocytes are important effectors of ADCC, suggesting further developments of this property in the context of cellular therapies for cancer and infectious diseases.

SUBMITTER: Yeap WH

PROVIDER: S-EPMC5037471 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes.

Yeap Wei Hseun WH Wong Kok Loon KL Shimasaki Noriko N Teo Esmeralda Chi Yuan EC Quek Jeffrey Kim Siang JK Yong Hao Xiang HX Diong Colin Phipps CP Bertoletti Antonio A Linn Yeh Ching YC Wong Siew Cheng SC

Scientific reports 20160927

Antibody-dependent cellular cytotoxicity (ADCC) is exerted by immune cells expressing surface Fcγ receptors (FcγRs) against cells coated with antibody, such as virus-infected or transformed cells. CD16, the FcγRIIIA, is essential for ADCC by NK cells, and is also expressed by a subset of human blood monocytes. We found that human CD16- expressing monocytes have a broad spectrum of ADCC capacities and can kill cancer cell lines, primary leukemic cells and hepatitis B virus-infected cells in the p ...[more]

PMID: 27670158

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Project description:Lifelong antiretroviral therapy (ART) for HIV-1 does not diminish the established latent reservoir. A possible cure approach is to reactivate the quiescent genome from latency and utilize immune responses to eliminate cells harboring reactivated HIV-1. It is not known whether antibodies within HIV-1-infected individuals can recognize and eliminate cells reactivated from latency through antibody-dependent cellular cytotoxicity (ADCC). We found that reactivation of HIV-1 expression in the latently infected ACH-2 cell line elicited antibody-mediated NK cell activation but did not result in antibody-mediated killing. The lack of CD4 expression on these HIV-1 envelope (Env)-expressing cells likely resulted in poor recognition of CD4-induced antibody epitopes on Env. To examine this further, cultured primary CD4(+) T cells from HIV-1(+) subjects were used as targets for ADCC. These ex vivo-expanded primary cells were modestly susceptible to ADCC mediated by autologous or heterologous HIV-1(+) serum antibodies. Importantly, ADCC mediated against these primary cells could be enhanced following incubation with a CD4-mimetic compound (JP-III-48) that exposes CD4-induced antibody epitopes on Env. Our studies suggest that with sufficient reactivation and expression of appropriate Env epitopes, primary HIV-1-infected cells can be targets for ADCC mediated by autologous serum antibodies and innate effector cells. The results of this study suggest that further investigation into the potential of ADCC to eliminate reactivated latently infected cells is warranted.An HIV-1 cure remains elusive due to the persistence of long-lived latently infected cells. An HIV-1 cure strategy, termed "shock and kill," aims to reactivate HIV-1 expression in latently infected cells and subsequently eliminate the reactivated cells through immune-mediated killing. While recent research efforts have focused on reversing HIV-1 latency, it remains unclear whether preexisting immune responses within HIV-1(+) individuals can efficiently eliminate the reactivated cells. HIV-1-specific antibodies can potentially eliminate cells reactivated from latency via Fc effector functions by recruiting innate immune cells. Our study highlights the potential role that antibody-dependent cellular cytotoxicity might play in antilatency cure approaches.

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CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes.

Publications

CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes.

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