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Persistence of Activated and Adaptive-Like NK Cells in HIV(+) Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy

Innate immune dysfunction persists in HIV(+) individuals despite effective combination antiretroviral therapy (cART). We recently demonstrated that an adaptive-like CD56(dim) NK cell population lacking the signal transducing protein FcRγ is expanded in HIV(+) individuals. Here, we analyzed a cohort...

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Autores principales: Hearps, Anna C., Agius, Paul A., Zhou, Jingling, Brunt, Samantha, Chachage, Mkunde, Angelovich, Thomas A., Cameron, Paul U., Giles, Michelle, Price, Patricia, Elliott, Julian, Jaworowski, Anthony
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491541/
https://www.ncbi.nlm.nih.gov/pubmed/28713370
http://dx.doi.org/10.3389/fimmu.2017.00731
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author Hearps, Anna C.
Agius, Paul A.
Zhou, Jingling
Brunt, Samantha
Chachage, Mkunde
Angelovich, Thomas A.
Cameron, Paul U.
Giles, Michelle
Price, Patricia
Elliott, Julian
Jaworowski, Anthony
author_facet Hearps, Anna C.
Agius, Paul A.
Zhou, Jingling
Brunt, Samantha
Chachage, Mkunde
Angelovich, Thomas A.
Cameron, Paul U.
Giles, Michelle
Price, Patricia
Elliott, Julian
Jaworowski, Anthony
author_sort Hearps, Anna C.
collection PubMed
description Innate immune dysfunction persists in HIV(+) individuals despite effective combination antiretroviral therapy (cART). We recently demonstrated that an adaptive-like CD56(dim) NK cell population lacking the signal transducing protein FcRγ is expanded in HIV(+) individuals. Here, we analyzed a cohort of HIV(+) men who have sex with men (MSM, n = 20) at baseline and following 6, 12, and 24 months of cART and compared them with uninfected MSM (n = 15) to investigate the impact of cART on NK cell dysfunction. Proportions of NK cells expressing markers of early (CD69(+)) and late (HLA-DR(+)/CD38(+)) activation were elevated in cART-naïve HIV(+) MSM (p = 0.004 and 0.015, respectively), as were FcRγ(−) NK cells (p = 0.003). Using latent growth curve modeling, we show that cART did not reduce levels of FcRγ(−) NK cells (p = 0.115) or activated HLA-DR(+)/CD38(+) NK cells (p = 0.129) but did reduce T cell and monocyte activation (p < 0.001 for all). Proportions of FcRγ(−) NK cells were not associated with NK cell, T cell, or monocyte activation, suggesting different factors drive CD56(dim) FcRγ(−) NK cell expansion and immune activation in HIV(+) individuals. While proportions of activated CD69(+) NK cells declined significantly on cART (p = 0.003), the rate was significantly slower than the decline of T cell and monocyte activation, indicating a reduced potency of cART against NK cell activation. Our findings indicate that 2 years of suppressive cART have no impact on CD56(dim) FcRγ(−) NK cell expansion and that NK cell activation persists after normalization of other immune parameters. This may have implications for the development of malignancies and co-morbidities in HIV(+) individuals on cART.
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spelling pubmed-54915412017-07-14 Persistence of Activated and Adaptive-Like NK Cells in HIV(+) Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy Hearps, Anna C. Agius, Paul A. Zhou, Jingling Brunt, Samantha Chachage, Mkunde Angelovich, Thomas A. Cameron, Paul U. Giles, Michelle Price, Patricia Elliott, Julian Jaworowski, Anthony Front Immunol Immunology Innate immune dysfunction persists in HIV(+) individuals despite effective combination antiretroviral therapy (cART). We recently demonstrated that an adaptive-like CD56(dim) NK cell population lacking the signal transducing protein FcRγ is expanded in HIV(+) individuals. Here, we analyzed a cohort of HIV(+) men who have sex with men (MSM, n = 20) at baseline and following 6, 12, and 24 months of cART and compared them with uninfected MSM (n = 15) to investigate the impact of cART on NK cell dysfunction. Proportions of NK cells expressing markers of early (CD69(+)) and late (HLA-DR(+)/CD38(+)) activation were elevated in cART-naïve HIV(+) MSM (p = 0.004 and 0.015, respectively), as were FcRγ(−) NK cells (p = 0.003). Using latent growth curve modeling, we show that cART did not reduce levels of FcRγ(−) NK cells (p = 0.115) or activated HLA-DR(+)/CD38(+) NK cells (p = 0.129) but did reduce T cell and monocyte activation (p < 0.001 for all). Proportions of FcRγ(−) NK cells were not associated with NK cell, T cell, or monocyte activation, suggesting different factors drive CD56(dim) FcRγ(−) NK cell expansion and immune activation in HIV(+) individuals. While proportions of activated CD69(+) NK cells declined significantly on cART (p = 0.003), the rate was significantly slower than the decline of T cell and monocyte activation, indicating a reduced potency of cART against NK cell activation. Our findings indicate that 2 years of suppressive cART have no impact on CD56(dim) FcRγ(−) NK cell expansion and that NK cell activation persists after normalization of other immune parameters. This may have implications for the development of malignancies and co-morbidities in HIV(+) individuals on cART. Frontiers Media S.A. 2017-06-30 /pmc/articles/PMC5491541/ /pubmed/28713370 http://dx.doi.org/10.3389/fimmu.2017.00731 Text en Copyright © 2017 Hearps, Agius, Zhou, Brunt, Chachage, Angelovich, Cameron, Giles, Price, Elliott and Jaworowski. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Hearps, Anna C.
Agius, Paul A.
Zhou, Jingling
Brunt, Samantha
Chachage, Mkunde
Angelovich, Thomas A.
Cameron, Paul U.
Giles, Michelle
Price, Patricia
Elliott, Julian
Jaworowski, Anthony
Persistence of Activated and Adaptive-Like NK Cells in HIV(+) Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy
title Persistence of Activated and Adaptive-Like NK Cells in HIV(+) Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy
title_full Persistence of Activated and Adaptive-Like NK Cells in HIV(+) Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy
title_fullStr Persistence of Activated and Adaptive-Like NK Cells in HIV(+) Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy
title_full_unstemmed Persistence of Activated and Adaptive-Like NK Cells in HIV(+) Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy
title_short Persistence of Activated and Adaptive-Like NK Cells in HIV(+) Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy
title_sort persistence of activated and adaptive-like nk cells in hiv(+) individuals despite 2 years of suppressive combination antiretroviral therapy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491541/
https://www.ncbi.nlm.nih.gov/pubmed/28713370
http://dx.doi.org/10.3389/fimmu.2017.00731
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