Magnitude and Kinetics of CD8[superscript +] T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point
Author(s)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; ... Show more Show less
Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point
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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.
DepartmentInstitute for Medical Engineering and Science; Massachusetts Institute of Technology. Department of Chemical Engineering; Ragon Institute of MGH, MIT and Harvard
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.