Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo.
Understanding the role of cytotoxic T lymphocytes (CTLs) in controlling HIV-1 infection is vital for vaccine design. However, it is difficult to assess the importance of CTLs in natural infection. Different human leukocyte antigen (HLA) class I alleles are associated with different rates of progress...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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2006
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| _version_ | 1797055090436079616 |
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| author | Asquith, B Edwards, C Lipsitch, M Mclean, A |
| author_facet | Asquith, B Edwards, C Lipsitch, M Mclean, A |
| author_sort | Asquith, B |
| collection | OXFORD |
| description | Understanding the role of cytotoxic T lymphocytes (CTLs) in controlling HIV-1 infection is vital for vaccine design. However, it is difficult to assess the importance of CTLs in natural infection. Different human leukocyte antigen (HLA) class I alleles are associated with different rates of progression to AIDS, indicating that CTLs play a protective role. Yet virus clearance rates following antiretroviral therapy are not impaired in individuals with advanced HIV disease, suggesting that weakening of the CTL response is not the major underlying cause of disease progression and that CTLs do not have an important protective role. Here we reconcile these apparently conflicting studies. We estimate the selection pressure exerted by CTL responses that drive the emergence of immune escape variants, thereby directly quantifying the efficiency of HIV-1-specific CTLs in vivo. We estimate that only 2% of productively infected CD4+ cell death is attributable to CTLs recognising a single epitope. We suggest that CTLs kill a large number of infected cells (about 10(7)) per day but are not responsible for the majority of infected cell death. |
| first_indexed | 2024-03-06T19:06:32Z |
| format | Journal article |
| id | oxford-uuid:15543278-b86c-4238-8e60-23c2f24c20b7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:06:32Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:15543278-b86c-4238-8e60-23c2f24c20b72022-03-26T10:24:48ZInefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:15543278-b86c-4238-8e60-23c2f24c20b7EnglishSymplectic Elements at Oxford2006Asquith, BEdwards, CLipsitch, MMclean, AUnderstanding the role of cytotoxic T lymphocytes (CTLs) in controlling HIV-1 infection is vital for vaccine design. However, it is difficult to assess the importance of CTLs in natural infection. Different human leukocyte antigen (HLA) class I alleles are associated with different rates of progression to AIDS, indicating that CTLs play a protective role. Yet virus clearance rates following antiretroviral therapy are not impaired in individuals with advanced HIV disease, suggesting that weakening of the CTL response is not the major underlying cause of disease progression and that CTLs do not have an important protective role. Here we reconcile these apparently conflicting studies. We estimate the selection pressure exerted by CTL responses that drive the emergence of immune escape variants, thereby directly quantifying the efficiency of HIV-1-specific CTLs in vivo. We estimate that only 2% of productively infected CD4+ cell death is attributable to CTLs recognising a single epitope. We suggest that CTLs kill a large number of infected cells (about 10(7)) per day but are not responsible for the majority of infected cell death. |
| spellingShingle | Asquith, B Edwards, C Lipsitch, M Mclean, A Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. |
| title | Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. |
| title_full | Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. |
| title_fullStr | Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. |
| title_full_unstemmed | Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. |
| title_short | Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. |
| title_sort | inefficient cytotoxic t lymphocyte mediated killing of hiv 1 infected cells in vivo |
| work_keys_str_mv | AT asquithb inefficientcytotoxictlymphocytemediatedkillingofhiv1infectedcellsinvivo AT edwardsc inefficientcytotoxictlymphocytemediatedkillingofhiv1infectedcellsinvivo AT lipsitchm inefficientcytotoxictlymphocytemediatedkillingofhiv1infectedcellsinvivo AT mcleana inefficientcytotoxictlymphocytemediatedkillingofhiv1infectedcellsinvivo |