Resting Regulatory CD4 T Cells: A Site of HIV Persistence in Patients on Long-Term Effective Antiretroviral Therapy

被引：78

作者：

Tran, Tu-Anh ^{[1
]}

de Herve, Marie-Ghislaine de Goer ^{[1
]}

Hendel-Chavez, Houria ^{[2
]}

Dembele, Bamory ^{[1
]}

Le Nevot, Emilie ^{[2
]}

Abbed, Karim ^{[2
]}

Pallier, Coralie ^{[4
]}

Goujard, Cecile ^{[1
,3
]}

Gasnault, Jacques ^{[1
,3
]}

Delfraissy, Jean-Francois ^{[1
,3
]}

Balazuc, Anne-Marie ^{[5
]}

Taoufik, Yassine ^{[1
,2
]}

机构：

[1] Univ Paris 11, INSERM, U802, Le Kremlin Bicetre, France

[2] AP HP, Hop Bicetre, Unite Immunol Biol, Le Kremlin Bicetre, France

[3] AP HP, Hop Bicetre, Serv Med Interne, Le Kremlin Bicetre, France

[4] AP HP, Hop Bicetre, Lab Virol, Le Kremlin Bicetre, France

[5] Inst Pasteur, Paris, France

来源：

PLOS ONE | 2008年 / 3卷 / 10期

关键词：

D O I：

10.1371/journal.pone.0003305

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background: In HIV-infected patients on long-term HAART, virus persistence in resting long-lived CD4 T cells is a major barrier to curing the infection. Cell quiescence, by favouring HIV latency, reduces the risk of recognition and cell destruction by cytotoxic lymphocytes. Several cell-activation-based approaches have been proposed to disrupt cell quiescence and then virus latency, but these approaches have not eradicated the virus. CD4(+)CD25(+) regulatory T cells (Tregs) are a CD4(+) T-cell subset with particular activation properties. We investigated the role of these cells in virus persistence in patients on long-term HAART. Methodology/Principal Findings: We found evidence of infection of resting Tregs (HLADR(-)CD69(-)CD25(hi)FoxP3(+)CD4(+) T cells) purified from patients on prolonged HAART. HIV DNA harbouring cells appear more abundant in the Treg subset than in non-Tregs. The half-life of the Treg reservoir was estimated at 20 months. Since Tregs from patients on prolonged HAART showed hyporesponsiveness to cell activation and inhibition of HIV-specific cytotoxic T lymphocyte-related functions upon activation, therapeutics targeting cell quiescence to induce virus expression may not be appropriate for purging the Treg reservoir. Conclusions: Our results identify Tregs as a particular compartment within the latent reservoir that may require a specific approach for its purging.

引用

页数：11