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 FcR? is expanded in HIV+ individuals. Here, we analyzed a cohort of...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
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Frontiers Research Foundation
2017
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| Online Access: | http://hdl.handle.net/20.500.11937/56798 |
| _version_ | 1848759941306777600 |
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| author | Hearps, A. Agius, P. Zhou, J. Brunt, S. Chachage, M. Angelovich, T. Cameron, P. Giles, M. Price, Patricia Elliott, J. Jaworowski, A. |
| author_facet | Hearps, A. Agius, P. Zhou, J. Brunt, S. Chachage, M. Angelovich, T. Cameron, P. Giles, M. Price, Patricia Elliott, J. Jaworowski, A. |
| author_sort | Hearps, A. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| 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 FcR? 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 FcR?- NK cells (p = 0.003). Using latent growth curve modeling, we show that cART did not reduce levels of FcR?- 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 FcR?- NK cells were not associated with NK cell, T cell, or monocyte activation, suggesting different factors drive CD56 dim FcR?- 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 FcR?- 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. |
| first_indexed | 2025-11-14T10:07:53Z |
| format | Journal Article |
| id | curtin-20.500.11937-56798 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:07:53Z |
| publishDate | 2017 |
| publisher | Frontiers Research Foundation |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-567982017-11-16T07:00:34Z Persistence of Activated and Adaptive-Like NK Cells in HIV+ Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy Hearps, A. Agius, P. Zhou, J. Brunt, S. Chachage, M. Angelovich, T. Cameron, P. Giles, M. Price, Patricia Elliott, J. Jaworowski, A. 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 FcR? 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 FcR?- NK cells (p = 0.003). Using latent growth curve modeling, we show that cART did not reduce levels of FcR?- 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 FcR?- NK cells were not associated with NK cell, T cell, or monocyte activation, suggesting different factors drive CD56 dim FcR?- 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 FcR?- 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. 2017 Journal Article http://hdl.handle.net/20.500.11937/56798 10.3389/fimmu.2017.00731 http://creativecommons.org/licenses/by/4.0/ Frontiers Research Foundation fulltext |
| spellingShingle | Hearps, A. Agius, P. Zhou, J. Brunt, S. Chachage, M. Angelovich, T. Cameron, P. Giles, M. Price, Patricia Elliott, J. Jaworowski, A. 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 |
| url | http://hdl.handle.net/20.500.11937/56798 |