title: Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point.
abstract: 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.
authors.affiliation: 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, Cambridge, MA 02139, USA.
authors.forename: Zaza M
authors.initials: ZM
authors.lastname: Ndhlovu
authors.affiliation: 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, Cambridge, MA 02139, USA.
authors.forename: Philomena
authors.initials: P
authors.lastname: Kamya
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
authors.forename: Nikoshia
authors.initials: N
authors.lastname: Mewalal
authors.affiliation: 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.
authors.forename: Henrik N
authors.initials: HN
authors.lastname: Kløverpris
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
authors.forename: Thandeka
authors.initials: T
authors.lastname: Nkosi
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
authors.forename: Karyn
authors.initials: K
authors.lastname: Pretorius
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
authors.forename: Faatima
authors.initials: F
authors.lastname: Laher
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
authors.forename: Funsho
authors.initials: F
authors.lastname: Ogunshola
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
authors.forename: Denis
authors.initials: D
authors.lastname: Chopera
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 25 Ames St, Cambridge, MA 02142, USA.
authors.forename: Karthik
authors.initials: K
authors.lastname: Shekhar
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
authors.forename: Musie
authors.initials: M
authors.lastname: Ghebremichael
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
authors.forename: Nasreen
authors.initials: N
authors.lastname: Ismail
authors.affiliation: 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, Cambridge, MA 02139, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Moodley
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford OX1 3SY, United Kingdom.
authors.forename: Amna
authors.initials: A
authors.lastname: Malik
authors.affiliation: 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, Durban, 4001, South Africa.
authors.forename: Alasdair
authors.initials: A
authors.lastname: Leslie
authors.affiliation: 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.
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Goulder
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, 2200-Copenhagen N, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Buus
authors.affiliation: 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.
authors.forename: Arup
authors.initials: A
authors.lastname: Chakraborty
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
authors.forename: Krista
authors.initials: K
authors.lastname: Dong
authors.affiliation: 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, Cambridge, MA 02139, USA; KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa; Max Planck Institute for Infection Biology, Chariteplatz 1, 10117, Berlin, Germany.
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
authors.affiliation: 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, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: bwalker@mgh.harvard.edu.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
mesh_terms: D000293:Adolescent; D017209:Apoptosis / Q000276:immunology; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology; D013997:Time Factors; D019562:Viral Load / Q000276:immunology*; D014766:Viremia / Q000175:diagnosis / Q000276:immunology; D055815:Young Adult; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D012367:RNA, Viral; D019014:fas Receptor