HIV-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) - Mediating Antibodies Decline while NK Cell Function Increases during Antiretroviral Therapy (ART)

Sanne Skov Jensen; Anders Fomsgaard; Marie Borggren; Jeanette Linnea Tingstedt; Jan Gerstoft; Gitte Kronborg; Line Dahlerup Rasmussen; Court Pedersen; Ingrid Karlsson

doi:10.1371/journal.pone.0145249

HIV-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) - Mediating Antibodies Decline while NK Cell Function Increases during Antiretroviral Therapy (ART)

Sanne Skov Jensen, Anders Fomsgaard, Marie Borggren, Jeanette Linnea Tingstedt, Jan Gerstoft, Gitte Kronborg, Line Dahlerup Rasmussen, Court Pedersen, Ingrid Karlsson

Department of Clinical Medicine

7 Citations (Scopus)

Abstract

Understanding alterations in HIV-specific immune responses during antiretroviral therapy (ART), such as antibody-dependent cellular cytotoxicity (ADCC), is important in the development of novel strategies to control HIV-1 infection. This study included 53 HIV-1 positive individuals. We evaluated the ability of effector cells and antibodies to mediate ADCC separately and in combination using the ADCC-PanToxiLux assay. The ability of the peripheral blood mononuclear cells (PBMCs) to mediate ADCC was significantly higher in individuals who had been treated with ART before seroconversion, compared to the individuals initiating ART at a low CD4+ T cell count (<350 cells/μl blood) and the ART-naïve individuals. The frequency of CD16 expressing natural killer (NK) cells correlated with both the duration of ART and Granzyme B (GzB) activity. In contrast, the plasma titer of antibodies mediating ADCC declined during ART. These findings suggest improved cytotoxic function of the NK cells if initiating ART early during infection, while the levels of ADCC mediating antibodies declined during ART.

Original language	English
Article number	e0145249
Journal	P L o S One
Volume	10
Issue number	12
Pages (from-to)	1-15
Number of pages	15
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0145249
Publication status	Published - Dec 2015

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Jensen, S. S., Fomsgaard, A., Borggren, M., Tingstedt, J. L., Gerstoft, J., Kronborg, G., Rasmussen, L. D., Pedersen, C., & Karlsson, I. (2015). HIV-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) - Mediating Antibodies Decline while NK Cell Function Increases during Antiretroviral Therapy (ART). P L o S One, 10(12), 1-15. [e0145249]. https://doi.org/10.1371/journal.pone.0145249

HIV-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) - Mediating Antibodies Decline while NK Cell Function Increases during Antiretroviral Therapy (ART). / Jensen, Sanne Skov; Fomsgaard, Anders; Borggren, Marie et al.

In: P L o S One, Vol. 10, No. 12, e0145249, 12.2015, p. 1-15.

Research output: Contribution to journal › Journal article › Research › peer-review

Jensen, SS, Fomsgaard, A, Borggren, M, Tingstedt, JL, Gerstoft, J , Kronborg, G, Rasmussen, LD, Pedersen, C & Karlsson, I 2015, 'HIV-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) - Mediating Antibodies Decline while NK Cell Function Increases during Antiretroviral Therapy (ART)', P L o S One, vol. 10, no. 12, e0145249, pp. 1-15. https://doi.org/10.1371/journal.pone.0145249

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abstract = "Understanding alterations in HIV-specific immune responses during antiretroviral therapy (ART), such as antibody-dependent cellular cytotoxicity (ADCC), is important in the development of novel strategies to control HIV-1 infection. This study included 53 HIV-1 positive individuals. We evaluated the ability of effector cells and antibodies to mediate ADCC separately and in combination using the ADCC-PanToxiLux assay. The ability of the peripheral blood mononuclear cells (PBMCs) to mediate ADCC was significantly higher in individuals who had been treated with ART before seroconversion, compared to the individuals initiating ART at a low CD4+ T cell count (<350 cells/μl blood) and the ART-na{\"i}ve individuals. The frequency of CD16 expressing natural killer (NK) cells correlated with both the duration of ART and Granzyme B (GzB) activity. In contrast, the plasma titer of antibodies mediating ADCC declined during ART. These findings suggest improved cytotoxic function of the NK cells if initiating ART early during infection, while the levels of ADCC mediating antibodies declined during ART.",

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AB - Understanding alterations in HIV-specific immune responses during antiretroviral therapy (ART), such as antibody-dependent cellular cytotoxicity (ADCC), is important in the development of novel strategies to control HIV-1 infection. This study included 53 HIV-1 positive individuals. We evaluated the ability of effector cells and antibodies to mediate ADCC separately and in combination using the ADCC-PanToxiLux assay. The ability of the peripheral blood mononuclear cells (PBMCs) to mediate ADCC was significantly higher in individuals who had been treated with ART before seroconversion, compared to the individuals initiating ART at a low CD4+ T cell count (<350 cells/μl blood) and the ART-naïve individuals. The frequency of CD16 expressing natural killer (NK) cells correlated with both the duration of ART and Granzyme B (GzB) activity. In contrast, the plasma titer of antibodies mediating ADCC declined during ART. These findings suggest improved cytotoxic function of the NK cells if initiating ART early during infection, while the levels of ADCC mediating antibodies declined during ART.

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HIV-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) - Mediating Antibodies Decline while NK Cell Function Increases during Antiretroviral Therapy (ART)

Abstract

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