Magnitude and Kinetics of CD8[superscript +] T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point
CD8[superscript +] T cells contribute to the control of HIV, but it is not clear whether initial immune responses modulate the viral set point. We screened high-risk uninfected women twice a week for plasma HIV RNA and identified 12 hyperacute infections. Onset of viremia elicited a massive HIV-spec...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier/Cell Press
2017
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| Online Access: | http://hdl.handle.net/1721.1/107652 https://orcid.org/0000-0003-1268-9602 |
| _version_ | 1826197447892795392 |
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| author | Ndhlovu, Zaza M. Kamya, Philomena Mewalal, Nikoshia Kløverpris, Henrik N. Nkosi, Thandeka Pretorius, Karyn Laher, Faatima Ogunshola, Funsho Chopera, Denis Ghebremichael, Musie Ismail, Nasreen Moodley, Amber Malik, Amna Leslie, Alasdair Goulder, Philip J.R. Buus, Søren Dong, Krista Ndung’u, Thumbi Walker, Bruce D. Chakraborty, Arup K Shekhar, Karthik |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Ndhlovu, Zaza M. Kamya, Philomena Mewalal, Nikoshia Kløverpris, Henrik N. Nkosi, Thandeka Pretorius, Karyn Laher, Faatima Ogunshola, Funsho Chopera, Denis Ghebremichael, Musie Ismail, Nasreen Moodley, Amber Malik, Amna Leslie, Alasdair Goulder, Philip J.R. Buus, Søren Dong, Krista Ndung’u, Thumbi Walker, Bruce D. Chakraborty, Arup K Shekhar, Karthik |
| author_sort | Ndhlovu, Zaza M. |
| collection | MIT |
| description | CD8[superscript +] T cells contribute to the control of HIV, but it is not clear whether initial immune responses modulate the viral set point. We screened high-risk uninfected women twice a week for plasma HIV RNA and identified 12 hyperacute infections. Onset of viremia elicited a massive HIV-specific CD8[superscript +] T cell response, with limited bystander activation of non-HIV memory CD8[superscript +] T cells. HIV-specific CD8[superscript +] T cells secreted little interferon-γ, underwent rapid apoptosis, and failed to upregulate the interleukin-7 receptor, known to be important for T cell survival. The rapidity to peak CD8[superscript +] T cell activation and the absolute magnitude of activation induced by the exponential rise in viremia were inversely correlated with set point viremia. These data indicate that rapid, high magnitude HIV-induced CD8[superscript +] T cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine design. |
| first_indexed | 2024-09-23T10:47:49Z |
| format | Article |
| id | mit-1721.1/107652 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:47:49Z |
| publishDate | 2017 |
| publisher | Elsevier/Cell Press |
| record_format | dspace |
| spelling | mit-1721.1/1076522022-09-30T23:06:45Z Magnitude and Kinetics of CD8[superscript +] T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point Ndhlovu, Zaza M. Kamya, Philomena Mewalal, Nikoshia Kløverpris, Henrik N. Nkosi, Thandeka Pretorius, Karyn Laher, Faatima Ogunshola, Funsho Chopera, Denis Ghebremichael, Musie Ismail, Nasreen Moodley, Amber Malik, Amna Leslie, Alasdair Goulder, Philip J.R. Buus, Søren Dong, Krista Ndung’u, Thumbi Walker, Bruce D. Chakraborty, Arup K Shekhar, Karthik Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Chemical Engineering Ragon Institute of MGH, MIT and Harvard Chakraborty, Arup K Shekhar, Karthik CD8[superscript +] T cells contribute to the control of HIV, but it is not clear whether initial immune responses modulate the viral set point. We screened high-risk uninfected women twice a week for plasma HIV RNA and identified 12 hyperacute infections. Onset of viremia elicited a massive HIV-specific CD8[superscript +] T cell response, with limited bystander activation of non-HIV memory CD8[superscript +] T cells. HIV-specific CD8[superscript +] T cells secreted little interferon-γ, underwent rapid apoptosis, and failed to upregulate the interleukin-7 receptor, known to be important for T cell survival. The rapidity to peak CD8[superscript +] T cell activation and the absolute magnitude of activation induced by the exponential rise in viremia were inversely correlated with set point viremia. These data indicate that rapid, high magnitude HIV-induced CD8[superscript +] T cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine design. Bill & Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery Witten Family Foundation Dan and Marjorie Sullivan Ursula Brunner Gary and Loren Cohen Mark and Lisa Schwartz Foundation, International AIDS Vaccine Initiative (UKZNRSA1001) National Institute of Allergy and Infectious Diseases (U.S.) (R37AI067073) Center for AIDS Research (P30 AI060354) 2017-03-22T19:08:59Z 2017-03-22T19:08:59Z 2015-09 2015-06 Article http://purl.org/eprint/type/JournalArticle 1074-7613 1097-4180 http://hdl.handle.net/1721.1/107652 Ndhlovu, Zaza M. et al. “Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point.” Immunity 43.3 (2015): 591–604. https://orcid.org/0000-0003-1268-9602 en_US http://dx.doi.org/10.1016/j.immuni.2015.08.012 Immunity Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier/Cell Press PMC |
| spellingShingle | Ndhlovu, Zaza M. Kamya, Philomena Mewalal, Nikoshia Kløverpris, Henrik N. Nkosi, Thandeka Pretorius, Karyn Laher, Faatima Ogunshola, Funsho Chopera, Denis Ghebremichael, Musie Ismail, Nasreen Moodley, Amber Malik, Amna Leslie, Alasdair Goulder, Philip J.R. Buus, Søren Dong, Krista Ndung’u, Thumbi Walker, Bruce D. Chakraborty, Arup K Shekhar, Karthik Magnitude and Kinetics of CD8[superscript +] T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point |
| title | Magnitude and Kinetics of CD8[superscript +] T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point |
| title_full | Magnitude and Kinetics of CD8[superscript +] T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point |
| title_fullStr | Magnitude and Kinetics of CD8[superscript +] T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point |
| title_full_unstemmed | Magnitude and Kinetics of CD8[superscript +] T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point |
| title_short | Magnitude and Kinetics of CD8[superscript +] T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point |
| title_sort | magnitude and kinetics of cd8 superscript t cell activation during hyperacute hiv infection impact viral set point |
| url | http://hdl.handle.net/1721.1/107652 https://orcid.org/0000-0003-1268-9602 |
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