Inhibitory Killer Immunoglobulin-like receptors to self HLA-B and HLA-C ligands contribute differentially to Natural Killer cell functional potential in HIV infected Slow Progressors

Ce manuscrit est une pré-publication d'un article paru dans Clinical Immunology 2012; 143(3): 246-255 url: http://www.journals.elsevier.com/clinical-immunology/IRSC et FRSQ - Réseau SIDA et maladies infectieuse

Magnitude and Kinetics of CD8+ 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-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 FoundationCollaboration for AIDS Vaccine DiscoveryWitten Family FoundationDan and Marjorie SullivanUrsula BrunnerGary and Loren CohenMark 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

T cell Activation does not drive CD4 decline in longitudinally followed HIV-infected Elite Controllers

Abstract Background Elite controllers (EC) are a rare subset of HIV infected individuals who control viral load below 50 copies/ml of plasma without treatment. Methods Thirty four EC were studied. The slope of CD4 count change was available for 25 of these subjects. We assessed immune activation by measuring the percent of CD38+HLA-DR+CD8+ T cells in the EC group and comparing it with that in 24 treatment-naïve HIV disease progressors and 13 HIV uninfected healthy controls. Results Compared to HIV uninfected subjects, EC had higher percentages of CD38+HLA-DR+CD8+ T cells (p < 0.001) that was lower than that observed in progressors (p < 0.01). Fifteen of 25 EC had a slope of CD4 count change that was not significantly different from 0 while 3 had a positive and 7 a negative CD4 count slope. Immune activation did not distinguish EC subsets with stable/increasing versus declining CD4 counts. Conclusions Elevated immune activation in ECs is not associated with a faster rate of CD4 declin

T cell Activation does not drive CD4 decline in longitudinally followed HIV-infected Elite Controllers

Abstract Background Elite controllers (EC) are a rare subset of HIV infected individuals who control viral load below 50 copies/ml of plasma without treatment. Methods Thirty four EC were studied. The slope of CD4 count change was available for 25 of these subjects. We assessed immune activation by measuring the percent of CD38+HLA-DR+CD8+ T cells in the EC group and comparing it with that in 24 treatment-naïve HIV disease progressors and 13 HIV uninfected healthy controls. Results Compared to HIV uninfected subjects, EC had higher percentages of CD38+HLA-DR+CD8+ T cells (p Conclusions Elevated immune activation in ECs is not associated with a faster rate of CD4 decline</p

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

CD8(+) T&nbsp;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&nbsp;cell response, with limited bystander activation of non-HIV memory CD8(+) T&nbsp;cells. HIV-specific CD8(+) T&nbsp;cells secreted little interferon-γ, underwent rapid apoptosis, and failed to upregulate the interleukin-7 receptor, known to be important for T&nbsp;cell survival. The rapidity to peak CD8(+) T&nbsp;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&nbsp;cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine design

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

CD8(+) T&nbsp;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&nbsp;cell response, with limited bystander activation of non-HIV memory CD8(+) T&nbsp;cells. HIV-specific CD8(+) T&nbsp;cells secreted little interferon-γ, underwent rapid apoptosis, and failed to upregulate the interleukin-7 receptor, known to be important for T&nbsp;cell survival. The rapidity to peak CD8(+) T&nbsp;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&nbsp;cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine design