Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point

Zaza M. Ndhlovu, Philomena Kamya, Nikoshia Mewalal, Henrik N. Kløverpris, Thandeka Nkosi, Karyn Pretorius, Faatima Laher, Funsho Ogunshola, Denis Chopera, Karthik Shekhar, Musie Ghebremichael, Nasreen Ismail, Amber Moodley, Amna Malik, Alasdair Leslie, Philip J.R. Goulder, Søren Buus, Arup Chakraborty, Krista Dong, Thumbi Ndung'uBruce D. Walker

Research output: Contribution to journalArticlepeer-review

192 Scopus citations

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.

Original languageEnglish
Article number3155
Pages (from-to)591-604
Number of pages14
JournalImmunity
Volume43
Issue number3
DOIs
StatePublished - 15 Sep 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.

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