Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection.
BACKGROUND: Rare human immunodeficiency virus type 1 (HIV-1)-infected individuals who maintain control of viremia without therapy show potent CD8+ T-cell-mediated suppression of viral replication in vitro. Whether this is a determinant of the rate of disease progression in viremic individuals is unk...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2012
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| _version_ | 1797098451489521664 |
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| author | Yang, H Wu, H Hancock, G Clutton, G Sande, N Xu, X Yan, H Huang, X Angus, B Kuldanek, K Fidler, S Denny, T Birks, J McMichael, A Dorrell, L |
| author_facet | Yang, H Wu, H Hancock, G Clutton, G Sande, N Xu, X Yan, H Huang, X Angus, B Kuldanek, K Fidler, S Denny, T Birks, J McMichael, A Dorrell, L |
| author_sort | Yang, H |
| collection | OXFORD |
| description | BACKGROUND: Rare human immunodeficiency virus type 1 (HIV-1)-infected individuals who maintain control of viremia without therapy show potent CD8+ T-cell-mediated suppression of viral replication in vitro. Whether this is a determinant of the rate of disease progression in viremic individuals is unknown. METHODS: We measured CD8+ T-cell-mediated inhibition of a heterologous HIV-1 isolate in 50 HIV-1-seropositive adults with diverse progression rates. Linear mixed models were used to determine whether CD8+ T-cell function could explain variation in the rate of CD4+ T-cell decline. RESULTS: There was a significant interaction between CD8+ T-cell antiviral activity in vitro and the rate of CD4+ T-cell decline in chronically infected individuals (P < .0001). In a second prospective analysis of recently infected subjects followed for up to 3 years, CD8+ T-cell antiviral activity strongly predicted subsequent CD4+ T-cell decline (P < .0001) and explained up to 73% of the interindividual variation in the CD4+ T-cell slope. In addition, it was inversely associated with viral load set point (r = -0.68 and P = .002). CONCLUSIONS: The antiviral inhibitory capacity of CD8+ T cells is highly predictive of CD4+ T-cell loss in early HIV-1 infection. It has potential as a benchmark of effective immunity in vaccine evaluation. |
| first_indexed | 2024-03-07T05:09:44Z |
| format | Journal article |
| id | oxford-uuid:db2942ff-ae11-49b3-be08-2f78a6c2e365 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:09:44Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:db2942ff-ae11-49b3-be08-2f78a6c2e3652022-03-27T09:08:27ZAntiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:db2942ff-ae11-49b3-be08-2f78a6c2e365EnglishSymplectic Elements at Oxford2012Yang, HWu, HHancock, GClutton, GSande, NXu, XYan, HHuang, XAngus, BKuldanek, KFidler, SDenny, TBirks, JMcMichael, ADorrell, LBACKGROUND: Rare human immunodeficiency virus type 1 (HIV-1)-infected individuals who maintain control of viremia without therapy show potent CD8+ T-cell-mediated suppression of viral replication in vitro. Whether this is a determinant of the rate of disease progression in viremic individuals is unknown. METHODS: We measured CD8+ T-cell-mediated inhibition of a heterologous HIV-1 isolate in 50 HIV-1-seropositive adults with diverse progression rates. Linear mixed models were used to determine whether CD8+ T-cell function could explain variation in the rate of CD4+ T-cell decline. RESULTS: There was a significant interaction between CD8+ T-cell antiviral activity in vitro and the rate of CD4+ T-cell decline in chronically infected individuals (P < .0001). In a second prospective analysis of recently infected subjects followed for up to 3 years, CD8+ T-cell antiviral activity strongly predicted subsequent CD4+ T-cell decline (P < .0001) and explained up to 73% of the interindividual variation in the CD4+ T-cell slope. In addition, it was inversely associated with viral load set point (r = -0.68 and P = .002). CONCLUSIONS: The antiviral inhibitory capacity of CD8+ T cells is highly predictive of CD4+ T-cell loss in early HIV-1 infection. It has potential as a benchmark of effective immunity in vaccine evaluation. |
| spellingShingle | Yang, H Wu, H Hancock, G Clutton, G Sande, N Xu, X Yan, H Huang, X Angus, B Kuldanek, K Fidler, S Denny, T Birks, J McMichael, A Dorrell, L Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection. |
| title | Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection. |
| title_full | Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection. |
| title_fullStr | Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection. |
| title_full_unstemmed | Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection. |
| title_short | Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection. |
| title_sort | antiviral inhibitory capacity of cd8 t cells predicts the rate of cd4 t cell decline in hiv 1 infection |
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