Inefficient Cytotoxic T Lymphocyte–Mediated Killing of HIV-1–Infected Cells In Vivo

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Inefficient Cytotoxic T Lymphocyte–Mediated Killing of HIV-1–Infected Cells In Vivo

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Title: Inefficient Cytotoxic T Lymphocyte–Mediated Killing of HIV-1–Infected Cells In Vivo
Author: Asquith, Becca; Edwards, Charles T. T; McLean, Angela R; Rowland-Jones, Sarah; Lipsitch, Marc

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Citation: Asquith, Becca, Charles T. T. Edwards, Marc Lipsitch, and Angela R. McLean. 2006. Inefficient cytotoxic T lymphocyte–mediated killing of HIV-1–infected cells in vivo. PLoS Biology 4(4): e90.
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Abstract: 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 CD4þ cell death is attributable to CTLs recognising a single epitope. We suggest that CTLs kill a large number of infected cells (about 107) per day but are not responsible for the majority of infected cell death.
Published Version: doi:10.1371/journal.pbio.0040090
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4593277
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