Augmentation of HIV-specific T cell function by immediate treatment of hyperacute HIV-1 infection

被引：52

作者：

Ndhlovu, Zaza M. ^{[1
,2
,3
,4
]}

Kazer, Samuel W. ^{[2
,5
,6
,7
,8
]}

Nkosi, Thandeka ^{[1
,4
]}

Ogunshola, Funsho ^{[1
,4
]}

Muema, Daniel M. ^{[1
]}

Anmole, Gursev ^{[9
]}

Swann, Shayda A. ^{[10
]}

Moodley, Amber ^{[4
]}

Dong, Krista ^{[2
]}

Reddy, Tarylee ^{[11
]}

Brockman, Mark A. ^{[9
,10
]}

Shalek, Alex K. ^{[2
,5
,6
,7
,8
]}

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

Walker, Bruce D. ^{[2
,3
,4
,5
,8
]}

机构：

[1] Africa Hlth Res Inst, ZA-4036 Durban, South Africa

[2] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA

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

[4] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa

[5] MIT, IMES, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[6] MIT, Dept Chem, Cambridge, MA 02139 USA

[7] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[8] Brd Inst MIT & Harvard, Cambridge, MA 02139 USA

[9] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada

[10] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada

[11] South Africa Med Res Council, ZA-4091 Durban, South Africa

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2019年 / 11卷 / 493期

基金：

美国国家科学基金会;

关键词：

ANTIRETROVIRAL THERAPY; VIRUS; VIREMIA; RESPONSES; EFFECTOR; EXPRESSION; DEPLETION; INDIVIDUALS; ASSOCIATION; LYMPHOCYTES;

D O I：

10.1126/scitranslmed.aau0528

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Sustained viremia after acute HIV infection is associated with profound CD4(+) T cell loss and exhaustion of HIV-specific CD8(+) T cell responses. To determine the impact of combination antiretroviral therapy (cART) on these processes, we examined the evolution of immune responses in acutely infected individuals initiating treatment before peak viremia. Immediate treatment of Fiebig stages I and II infection led to a rapid decline in viral load and diminished magnitude of HIV-specific (tetramer(+)) CD8(+) T cell responses compared to untreated donors. There was a strong positive correlation between cumulative viral antigen exposure before full cART-induced suppression and immune responses measured by MHC class I tetramers, IFN-gamma ELISPOT, and CD8(+) T cell activation. HIV-specific CD8(+) T responses of early treated individuals were characterized by increased CD127 and BCL-2 expression, greater in vitro IFN-gamma secretion, and enhanced differentiation into effector memory (T-em) cells. Transcriptional analysis of tetramer(+) CD8(+) T cells from treated persons revealed reduced expression of genes associated with activation and apoptosis, with concurrent up-regulation of prosurvival genes including BCL-2, AXL, and SRC. Early treatment also resulted in robust HIV-specific CD4(+) T cell responses compared to untreated HIV-infected individuals. Our data show that limiting acute viremia results in enhanced functionality of HIV-specific CD4(+) and CD8(+) T cells, preserving key antiviral properties of these cells.

引用

页数：15