Composition and function of T cell subpopulations are slow to change despite effective antiretroviral treatment of HIV disease.
The ability to reconstitute a normal immune system with antiretroviral therapy in the setting of HIV infection remains uncertain. This study aimed to characterize quantitative and qualitative aspects of various T cell subpopulations that do not improve despite effective ART. CD4∶CD8 ratio was evalua...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3897457?pdf=render |
| _version_ | 1819181784473010176 |
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| author | Brinda Emu Walter J Moretto Rebecca Hoh Melissa Krone Jeffrey N Martin Douglas F Nixon Steven G Deeks Joseph M McCune |
| author_facet | Brinda Emu Walter J Moretto Rebecca Hoh Melissa Krone Jeffrey N Martin Douglas F Nixon Steven G Deeks Joseph M McCune |
| author_sort | Brinda Emu |
| collection | DOAJ |
| description | The ability to reconstitute a normal immune system with antiretroviral therapy in the setting of HIV infection remains uncertain. This study aimed to characterize quantitative and qualitative aspects of various T cell subpopulations that do not improve despite effective ART. CD4∶CD8 ratio was evaluated in HIV-infected subjects with viral loads >10,000 copies/µl ("non-controllers", n = 42), those with undetectable viral loads on ART ("ART-suppressed", n = 53), and HIV-uninfected subjects (n = 22). In addition, T cell phenotype and function were examined in 25 non-controllers, 18 ART-suppressed, and 7 HIV-uninfected subjects. CD4∶CD8 ratio in non-controllers, ART-suppressed, and HIV-uninfected subjects was 0.25, 0.48, and 1.95 respectively (P<0.0001 for all comparisons). The increased ratio in ART-suppressed compared to non-controllers was driven by an increase of CD4+ T cells, with no change in the expanded CD8+ T cell population. Expansion of differentiated (CD28-CD27-CD45RA+/-CCR7-) T cell subpopulations persisted despite ART and minimal changes were noted in naïve T cell frequencies over time. Increased number of CD8+CD28- T cells and increased CD8+ CMV-specific T cell responses were associated with a decreased CD4∶CD8 ratio. Measures of T cell function demonstrated persistence of high frequencies of CD8+ T cells producing IFN-γ. Lastly, though all CD8+ subpopulations demonstrated significantly lower Ki67 expression in ART-suppressed subjects, CD4+ T cell subpopulations did not consistently show this decrease, thus demonstrating different proliferative responses in the setting of T cell depletion. In summary, this study demonstrated that CD4∶CD8 ratios remained significantly decreased and naïve T cell numbers were slow to increase despite long-term viral suppression on ART. In addition, there is a evidence of differential regulation of the CD4+ and CD8+ T cell subpopulations, suggesting independent homeostatic regulation of the two compartments. |
| first_indexed | 2024-12-22T22:35:44Z |
| format | Article |
| id | doaj.art-5be25b4023fd48e089b4316c51a28abe |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T22:35:44Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5be25b4023fd48e089b4316c51a28abe2022-12-21T18:10:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8561310.1371/journal.pone.0085613Composition and function of T cell subpopulations are slow to change despite effective antiretroviral treatment of HIV disease.Brinda EmuWalter J MorettoRebecca HohMelissa KroneJeffrey N MartinDouglas F NixonSteven G DeeksJoseph M McCuneThe ability to reconstitute a normal immune system with antiretroviral therapy in the setting of HIV infection remains uncertain. This study aimed to characterize quantitative and qualitative aspects of various T cell subpopulations that do not improve despite effective ART. CD4∶CD8 ratio was evaluated in HIV-infected subjects with viral loads >10,000 copies/µl ("non-controllers", n = 42), those with undetectable viral loads on ART ("ART-suppressed", n = 53), and HIV-uninfected subjects (n = 22). In addition, T cell phenotype and function were examined in 25 non-controllers, 18 ART-suppressed, and 7 HIV-uninfected subjects. CD4∶CD8 ratio in non-controllers, ART-suppressed, and HIV-uninfected subjects was 0.25, 0.48, and 1.95 respectively (P<0.0001 for all comparisons). The increased ratio in ART-suppressed compared to non-controllers was driven by an increase of CD4+ T cells, with no change in the expanded CD8+ T cell population. Expansion of differentiated (CD28-CD27-CD45RA+/-CCR7-) T cell subpopulations persisted despite ART and minimal changes were noted in naïve T cell frequencies over time. Increased number of CD8+CD28- T cells and increased CD8+ CMV-specific T cell responses were associated with a decreased CD4∶CD8 ratio. Measures of T cell function demonstrated persistence of high frequencies of CD8+ T cells producing IFN-γ. Lastly, though all CD8+ subpopulations demonstrated significantly lower Ki67 expression in ART-suppressed subjects, CD4+ T cell subpopulations did not consistently show this decrease, thus demonstrating different proliferative responses in the setting of T cell depletion. In summary, this study demonstrated that CD4∶CD8 ratios remained significantly decreased and naïve T cell numbers were slow to increase despite long-term viral suppression on ART. In addition, there is a evidence of differential regulation of the CD4+ and CD8+ T cell subpopulations, suggesting independent homeostatic regulation of the two compartments.http://europepmc.org/articles/PMC3897457?pdf=render |
| spellingShingle | Brinda Emu Walter J Moretto Rebecca Hoh Melissa Krone Jeffrey N Martin Douglas F Nixon Steven G Deeks Joseph M McCune Composition and function of T cell subpopulations are slow to change despite effective antiretroviral treatment of HIV disease. PLoS ONE |
| title | Composition and function of T cell subpopulations are slow to change despite effective antiretroviral treatment of HIV disease. |
| title_full | Composition and function of T cell subpopulations are slow to change despite effective antiretroviral treatment of HIV disease. |
| title_fullStr | Composition and function of T cell subpopulations are slow to change despite effective antiretroviral treatment of HIV disease. |
| title_full_unstemmed | Composition and function of T cell subpopulations are slow to change despite effective antiretroviral treatment of HIV disease. |
| title_short | Composition and function of T cell subpopulations are slow to change despite effective antiretroviral treatment of HIV disease. |
| title_sort | composition and function of t cell subpopulations are slow to change despite effective antiretroviral treatment of hiv disease |
| url | http://europepmc.org/articles/PMC3897457?pdf=render |
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