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

被引：207

作者：

Ndhlovu, Zaza M. ^{[1
,2
]}

Kamya, Philomena ^{[1
,2
]}

Mewalal, Nikoshia ^{[1
]}

Kloverpris, Henrik N. ^{[3
,8
]}

Nkosi, Thandeka ^{[1
]}

Pretorius, Karyn ^{[1
]}

Laher, Faatima ^{[1
]}

Ogunshola, Funsho ^{[1
]}

Chopera, Denis ^{[3
]}

Shekhar, Karthik

Ghebremichael, Musie ^{[2
]}

Ismail, Nasreen ^{[1
]}

Moodley, Amber ^{[1
,2
]}

Malik, Amna ^{[7
]}

Leslie, Alasdair ^{[2
,3
]}

Goulder, Philip J. R. ^{[1
,7
]}

Buus, Soren ^{[8
]}

Chakraborty, Arup ^{[2
,6
]}

Dong, Krista ^{[2
]}

Ndung'u, Thumbi ^{[1
,2
,3
,4
]}

Walker, Bruce D. ^{[1
,2
,5
]}

机构：

[1] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4001 Durban, South Africa

[2] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA

[3] Univ KwaZulu Natal, Nelson R Mandela Sch Med, KwaZulu Natal Res Inst TB & HIV K RITH, ZA-4001 Durban, South Africa

[4] Max Planck Inst Infect Biol, D-10117 Berlin, Germany

[5] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[6] MIT, Dept Chem Engn, Cambridge, MA 02142 USA

[7] Univ Oxford, Dept Paediat, Oxford OX1 3SY, England

[8] Univ Copenhagen, Dept Immunol & Microbiol, DK-2200 Copenhagen N, Denmark

来源：

IMMUNITY | 2015年 / 43卷 / 03期

关键词：

IMMUNODEFICIENCY VIRUS-INFECTION; ANTIRETROVIRAL THERAPY; IMMUNE-RESPONSES; VIREMIA; EXPRESSION; EXPANSION; ANTIBODY; ESCAPE; AIDS; SEROCONVERSION;

D O I：

10.1016/j.immuni.2015.08.012

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-gamma, 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.

引用

页码：591 / 604

页数：14

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