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

View Article: PubMed Central - PubMed

ABSTRACT

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 presence of specific antibodies. Engagement of CD16 on monocytes by antibody bound to target cells activated β2-integrins and induced TNFα secretion. In turn, this induced TNFR expression on the target cells, making them susceptible to TNFα-mediated cell death. Treatment with TLR agonists, DAMPs or cytokines, such as IFNγ, 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.

No MeSH data available.


Related in: MedlinePlus

CD16+ monocytes from healthy individuals are able to perform ADCC on Rtx-coated primary B leukemic cells.ADCC by CD16+ monocytes from three healthy individuals on primary B leukaemic cells isolated from three B-CLL patients (A–C) either uncoated (dotted lines) or coated with Rtx (solid lines) at the indicated E:T ratios. All data plotted are mean ± SD of triplicate wells for each experiment. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001 and ****p ≤ 0.0001 with respect to uncoated leukaemic cells at the respective E:T ratios and based on Two-way ANOVA (****p ≤ 0.0001).
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f2: CD16+ monocytes from healthy individuals are able to perform ADCC on Rtx-coated primary B leukemic cells.ADCC by CD16+ monocytes from three healthy individuals on primary B leukaemic cells isolated from three B-CLL patients (A–C) either uncoated (dotted lines) or coated with Rtx (solid lines) at the indicated E:T ratios. All data plotted are mean ± SD of triplicate wells for each experiment. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001 and ****p ≤ 0.0001 with respect to uncoated leukaemic cells at the respective E:T ratios and based on Two-way ANOVA (****p ≤ 0.0001).

Mentions: Rituximab is commonly used for the treatment of B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia (B-CLL)2728. We assessed the capacity of CD16+ monocytes to exert ADCC against primary CD20+ leukemic cells from patients with B-CLL. Leukemic cells were isolated from either bone marrow (Fig. 2A,B) or peripheral blood (Fig. 2C) from three B-CLL patients. These cells were co-cultured at various E:T ratios with CD16+ monocytes isolated from healthy donors and substantial lysis of the CD20+ primary B-CLL cells in an antibody-dependent manner was observed (Fig. 2; solid lines versus dotted lines).


CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes
CD16+ monocytes from healthy individuals are able to perform ADCC on Rtx-coated primary B leukemic cells.ADCC by CD16+ monocytes from three healthy individuals on primary B leukaemic cells isolated from three B-CLL patients (A–C) either uncoated (dotted lines) or coated with Rtx (solid lines) at the indicated E:T ratios. All data plotted are mean ± SD of triplicate wells for each experiment. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001 and ****p ≤ 0.0001 with respect to uncoated leukaemic cells at the respective E:T ratios and based on Two-way ANOVA (****p ≤ 0.0001).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037471&req=5

f2: CD16+ monocytes from healthy individuals are able to perform ADCC on Rtx-coated primary B leukemic cells.ADCC by CD16+ monocytes from three healthy individuals on primary B leukaemic cells isolated from three B-CLL patients (A–C) either uncoated (dotted lines) or coated with Rtx (solid lines) at the indicated E:T ratios. All data plotted are mean ± SD of triplicate wells for each experiment. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001 and ****p ≤ 0.0001 with respect to uncoated leukaemic cells at the respective E:T ratios and based on Two-way ANOVA (****p ≤ 0.0001).
Mentions: Rituximab is commonly used for the treatment of B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia (B-CLL)2728. We assessed the capacity of CD16+ monocytes to exert ADCC against primary CD20+ leukemic cells from patients with B-CLL. Leukemic cells were isolated from either bone marrow (Fig. 2A,B) or peripheral blood (Fig. 2C) from three B-CLL patients. These cells were co-cultured at various E:T ratios with CD16+ monocytes isolated from healthy donors and substantial lysis of the CD20+ primary B-CLL cells in an antibody-dependent manner was observed (Fig. 2; solid lines versus dotted lines).

View Article: PubMed Central - PubMed

ABSTRACT

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 presence of specific antibodies. Engagement of CD16 on monocytes by antibody bound to target cells activated β2-integrins and induced TNFα secretion. In turn, this induced TNFR expression on the target cells, making them susceptible to TNFα-mediated cell death. Treatment with TLR agonists, DAMPs or cytokines, such as IFNγ, 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.

No MeSH data available.


Related in: MedlinePlus