ScIentIFIc RePoRTs | 7: 16799 | DOI:10.1038/s41598-017-17057-y
Peripheral T follicular helper Cells
Make a Dierence in HIV Reservoir
Size between Elite Controllers and
Patients on Successful cART
, Miguel Górgolas
, Alfonso Cabello
, Vicente Estrada
, José Manuel Ligos
, Carlos Barros
, Juan Carlos López-Bernaldo
, Francisco Javier
De La Hera
, María Montoya
, José Miguel Benito
& Norma Rallón
HIV latency is the main barrier to HIV eradication. Peripheral T follicular helper (pT) cells have a
prominent role in HIV persistence. Herein, we analyzed the HIV reservoir size within memory CD4+
T-cell subsets in patients with HIV replication control. Twenty HIV-infected patients with suppressed
HIV replication were included, with 10 elite controllers (EC) and 10 treated (TX) individuals. The HIV
reservoir size was analyzed in resting memory CD4+ T-cells (Trm), pT, and non-pT cells using an
ultrasensitive digital-droplet-PCR assay. Inter-group and intra-group dierences were tested using
non-parametric tests. Compared with the TX patients, the EC patients had smaller HIV reservoir not
only in Trm but also in pT and non-pT subsets of memory CD4+ T-cells. The largest dierences were
observed in pT cells (p = 0.025). The pT and non-pT cells harbored similar levels of HIV-DNA in the
EC (p = 0.60) and TX patients (p = 0.17); however, the contribution to HIV-DNA levels in memory CD4+
T-cells varied among the pT and non-pT subsets in both groups of patients. The EC patients showed
smaller HIV reservoir in memory CD4+ cells, especially in the pT subset, a population of cells with a
pivotal role in the antiviral immune response, suggesting a potential link between low levels of infection
in pT cells and the ability of the EC patients to spontaneously control HIV replication.
e HIV latent reservoir is the main barrier to HIV eradication. Although combination antiretroviral therapy
(cART) can eectively block viral replication in the host and reduce the circulating virus to undetectable levels
antiviral therapy cannot completely eliminate the virus from the human body. As a result, the viral load rapidly
rebounds within 2 to 8 weeks aer cART discontinuation
. e rebound occurs due to the presence of anatomic
reservoirs that drugs cannot easily access
. Additionally, there are reservoirs containing cells with HIV integrated
into the cell genome. However, the viral genome is transcriptionally silent, and the virus is refractory to both
cART and the immune system
e cellular reservoir may include several cell subpopulations, and the latent and long-term persistent virus
has been described in resting memory CD4+ T-cells (Trm cells)
. is CD4+ T-cell subset with memory pheno-
type (CD45RO+) and low expression of activation markers such as HLA-DR, CD25 or CD69
allow the estab-
lishment of latent reservoir extremely stable with a mean half-life of around 44 months
. ere is another
memory CD4+ T-cell subpopulation present in germinal centers, T follicular helper (T) cells. T cells have a
prominent role in regulating the HIV reservoir by supporting persistent infection, replication, and production of
HIV in both viremic HIV-infected subjects
and long-term cART-treated aviremic individuals
. T cells are a
memory CD4+ T-cell subset expressing CXCR5 and have B cell helper function localized within secondary lym-
. e counterpart in peripheral blood is called the peripheral T (pT) cells because they display
Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM),
28040, Madrid, Spain.
Hospital Universitario Rey Juan Carlos, 28933, Móstoles, Spain.
Fundación Jiménez Díaz, 28040, Madrid, Spain.
Hospital Universitario Clínico San Carlos, 28040, Madrid, Spain.
Celomics Unit, Centro Nacional de Investigaciones Cardiovasculares, 28029, Madrid, Spain.
de Móstoles, 28935, Móstoles, Spain.
Hospital General Universitario Gregorio Marañón, 28007, Madrid, Spain.
Correspondence and requests for materials should be addressed to J.M.B. (email: email@example.com) or N.R.
Received: 9 June 2017
Accepted: 21 November 2017
Published: xx xx xxxx