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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; Shekhar, Karthik; Ghebremichael, Musie; Ismail, Nasreen; Moodley, Amber; Malik, Amna; Leslie, Alasdair; Goulder, Philip J R; Buus, Søren; Chakraborty, Arup; Dong, Krista; Ndung'u, Thumbi; Walker, Bruce D.
Affiliation
  • Ndhlovu ZM; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, C
  • Kamya P; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, C
  • Mewalal N; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
  • Kløverpris HN; KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa; Department of Immunology and Microbiology, University of Copenhagen, 2200-Copenhagen N, Denmark.
  • Nkosi T; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
  • Pretorius K; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
  • Laher F; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
  • Ogunshola F; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
  • Chopera D; KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
  • Shekhar K; Department of Chemical Engineering, Massachusetts Institute of Technology, 25 Ames St, Cambridge, MA 02142, USA.
  • Ghebremichael M; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Ismail N; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
  • Moodley A; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, C
  • Malik A; Department of Paediatrics, University of Oxford, Oxford OX1 3SY, United Kingdom.
  • Leslie A; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA; KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Du
  • Goulder PJ; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa; Department of Paediatrics, University of Oxford, Oxford OX1 3SY, United Kingdom.
  • Buus S; Department of Immunology and Microbiology, University of Copenhagen, 2200-Copenhagen N, Denmark.
  • Chakraborty A; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, 25 Ames St, Cambridge, MA 02142, USA.
  • Dong K; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Ndung'u T; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, C
  • Walker BD; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, C
Immunity ; 43(3): 591-604, 2015 Sep 15.
Article in En | MEDLINE | ID: mdl-26362266
CD8(+) 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(+) T cell response, with limited bystander activation of non-HIV memory CD8(+) T cells. HIV-specific CD8(+) 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(+) 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(+) T cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine design.
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Full text: 1 Database: MEDLINE Main subject: Lymphocyte Activation / HIV Infections / CD8-Positive T-Lymphocytes / Viral Load Type of study: Diagnostic_studies / Prognostic_studies Limits: Adolescent / Adult / Female / Humans Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2015 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Lymphocyte Activation / HIV Infections / CD8-Positive T-Lymphocytes / Viral Load Type of study: Diagnostic_studies / Prognostic_studies Limits: Adolescent / Adult / Female / Humans Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2015 Type: Article