Peripheral T follicular helper Cells Make a Difference in HIV Reservoir Size between Elite Controllers and Patients on Successful cART

Marcial García,Norma Rallón,María Montoya,José Miguel Benito,Manuel Fernández-Guerrero,José Manuel Ligos,Francisco Javier De La Hera,Miguel Górgolas,Vicente Estrada,Juan Carlos López-Bernaldo,Alfonso Cabello,Carlos Barros

doi:10.1038/s41598-017-17057-y

Abstract

HIV latency is the main barrier to HIV eradication. Peripheral T follicular helper (pTfh) 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), pTfh, and non-pTfh cells using an ultrasensitive digital-droplet-PCR assay. Inter-group and intra-group differences 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 pTfh and non-pTfh subsets of memory CD4+ T-cells. The largest differences were observed in pTfh cells (p = 0.025). The pTfh and non-pTfh 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 pTfh and non-pTfh subsets in both groups of patients. The EC patients showed smaller HIV reservoir in memory CD4+ cells, especially in the pTfh subset, a population of cells with a pivotal role in the antiviral immune response, suggesting a potential link between low levels of infection in pTfh cells and the ability of the EC patients to spontaneously control HIV replication.

Highlights

The 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
We found the HIV reservoir size in peripheral Tfh (pTfh) cells was significantly lower in patients able to spontaneously control HIV replication (88 [33–291] copies/million cells) than that in patients with combination of antiretroviral therapy (cART)-mediated viral suppression (723 [393–1,199] copies/ million cells; p = 0.025) (Fig. 1a)
This difference between Elite controller (EC) and TX patients was less pronounced in non-pTfh cells (162 [,871] vs. 989 [600–1,354]) and was not significant (p = 0.172) (Fig. 1a)

Summary

Introduction

The 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). The 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)9 This CD4+ T-cell subset with memory phenotype (CD45RO+) and low expression of activation markers such as HLA-DR, CD25 or CD699 allow the establishment of latent reservoir extremely stable with a mean half-life of around 44 months. A few recent studies evaluated their ability to maintain better control of the HIV reservoir size29–31 These studies mostly used peripheral blood mononuclear cells (PBMCs) and resting CD4+ T-cell subsets. We examined the Trm cells, pTfh cells, and non-pTfh cells from EC patients and compared the results with those from treatment-controlled HIV-patients (TX, aviremic patients with cART)

Methods

Results

Conclusion