Direct ex vivo analysis reveals distinct phenotypic patterns of HIV-specific CD8(+) T lymphocyte activation in response to therapeutic manipulation of virus load.
Therapeutic intervention with antiretroviral therapy (ART) enables the modulation of HIV virus load and hence provides a unique opportunity to study the consequences of varying antigen load on the phenotype of virus-specific CD8(+) T lymphocytes in a persistent human viral infection. The recent adve...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2001
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| _version_ | 1826280150656876544 |
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| author | Oxenius, A Günthard, H Hirschel, B Fidler, S Weber, J Easterbrook, P Bell, J Phillips, R Price, D |
| author_facet | Oxenius, A Günthard, H Hirschel, B Fidler, S Weber, J Easterbrook, P Bell, J Phillips, R Price, D |
| author_sort | Oxenius, A |
| collection | OXFORD |
| description | Therapeutic intervention with antiretroviral therapy (ART) enables the modulation of HIV virus load and hence provides a unique opportunity to study the consequences of varying antigen load on the phenotype of virus-specific CD8(+) T lymphocytes in a persistent human viral infection. The recent advent of tetrameric peptide / HLA class I complexes has enabled the direct phenotypic characterization of antigen-specific T cell populations ex vivo. Here, we use this technology to examine directly ex vivo the consequences of therapeutic manipulation of HIV virus load on the phenotype of HIV-specific CTL. Our observations show that: (1) distinct sequential activation patterns of CD8(+) T cells are associated with increasing virus load; (2) T cell receptor (TCR) down-regulation without apoptosis represents an early event during the generation of a T cell response in a natural infection and precedes the emergence of two distinct antigen-specific CD8(+) T cell populations which differ in TCR and CD8 expression levels. Clear differences in surface Annexin V staining were observed between these populations. The observation that CTL activation, demonstrated by TCR and CD8 down-regulation, in response to rising levels of virus load, co-segregates with apoptosis only during later stages of the response indicates that antigen-associated cell death is restricted to distinct subpopulations of CTL. |
| first_indexed | 2024-03-07T00:09:24Z |
| format | Journal article |
| id | oxford-uuid:78afbac4-7c8b-48ad-a405-20d4a05c55e2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:09:24Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:78afbac4-7c8b-48ad-a405-20d4a05c55e22022-03-26T20:32:23ZDirect ex vivo analysis reveals distinct phenotypic patterns of HIV-specific CD8(+) T lymphocyte activation in response to therapeutic manipulation of virus load.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:78afbac4-7c8b-48ad-a405-20d4a05c55e2EnglishSymplectic Elements at Oxford2001Oxenius, AGünthard, HHirschel, BFidler, SWeber, JEasterbrook, PBell, JPhillips, RPrice, DTherapeutic intervention with antiretroviral therapy (ART) enables the modulation of HIV virus load and hence provides a unique opportunity to study the consequences of varying antigen load on the phenotype of virus-specific CD8(+) T lymphocytes in a persistent human viral infection. The recent advent of tetrameric peptide / HLA class I complexes has enabled the direct phenotypic characterization of antigen-specific T cell populations ex vivo. Here, we use this technology to examine directly ex vivo the consequences of therapeutic manipulation of HIV virus load on the phenotype of HIV-specific CTL. Our observations show that: (1) distinct sequential activation patterns of CD8(+) T cells are associated with increasing virus load; (2) T cell receptor (TCR) down-regulation without apoptosis represents an early event during the generation of a T cell response in a natural infection and precedes the emergence of two distinct antigen-specific CD8(+) T cell populations which differ in TCR and CD8 expression levels. Clear differences in surface Annexin V staining were observed between these populations. The observation that CTL activation, demonstrated by TCR and CD8 down-regulation, in response to rising levels of virus load, co-segregates with apoptosis only during later stages of the response indicates that antigen-associated cell death is restricted to distinct subpopulations of CTL. |
| spellingShingle | Oxenius, A Günthard, H Hirschel, B Fidler, S Weber, J Easterbrook, P Bell, J Phillips, R Price, D Direct ex vivo analysis reveals distinct phenotypic patterns of HIV-specific CD8(+) T lymphocyte activation in response to therapeutic manipulation of virus load. |
| title | Direct ex vivo analysis reveals distinct phenotypic patterns of HIV-specific CD8(+) T lymphocyte activation in response to therapeutic manipulation of virus load. |
| title_full | Direct ex vivo analysis reveals distinct phenotypic patterns of HIV-specific CD8(+) T lymphocyte activation in response to therapeutic manipulation of virus load. |
| title_fullStr | Direct ex vivo analysis reveals distinct phenotypic patterns of HIV-specific CD8(+) T lymphocyte activation in response to therapeutic manipulation of virus load. |
| title_full_unstemmed | Direct ex vivo analysis reveals distinct phenotypic patterns of HIV-specific CD8(+) T lymphocyte activation in response to therapeutic manipulation of virus load. |
| title_short | Direct ex vivo analysis reveals distinct phenotypic patterns of HIV-specific CD8(+) T lymphocyte activation in response to therapeutic manipulation of virus load. |
| title_sort | direct ex vivo analysis reveals distinct phenotypic patterns of hiv specific cd8 t lymphocyte activation in response to therapeutic manipulation of virus load |
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