Resting regulatory CD4 T cells: a site of HIV persistence in patients on long-term effective antiretroviral therapy.
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.


RESULTS
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.
Tran
Tu-Anh
TA
INSERM U802, Université Paris 11, Le Kremlin Bicêtre, France.
de Goër de Herve
Marie-Ghislaine
MG
Hendel-Chavez
Houria
H
Dembele
Bamory
B
Le Névot
Emilie
E
Abbed
Karim
K
Pallier
Coralie
C
Goujard
Cécile
C
Gasnault
Jacques
J
Delfraissy
Jean-François
JF
Balazuc
Anne-Marie
AM
Taoufik
Yassine
Y
D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D004197:Disease Reservoirs; D006678:HIV / Q000302:isolation & purification*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction