@ARTICLE{10.3389/fimmu.2016.00134, AUTHOR={Lu, Wei and Chen, Song and Lai, Chunhui and Lai, Mingyue and Fang, Hua and Dao, Hong and Kang, Jun and Fan, Jianhua and Guo, Weizhong and Fu, Linchun and Andrieu, Jean-Marie}, TITLE={Suppression of HIV Replication by CD8+ Regulatory T-Cells in Elite Controllers}, JOURNAL={Frontiers in Immunology}, VOLUME={7}, YEAR={2016}, URL={https://www.frontiersin.org/articles/10.3389/fimmu.2016.00134}, DOI={10.3389/fimmu.2016.00134}, ISSN={1664-3224}, ABSTRACT={We previously demonstrated in the Chinese macaque model that an oral vaccine made of inactivated SIV and Lactobacillus plantarum induced CD8+ regulatory T-cells, which suppressed the activation of SIV+CD4+ T-cells, prevented SIV replication, and protected macaques from SIV challenges. Here, we sought whether a similar population of CD8+ T-regs would induce the suppression of HIV replication in elite controllers (ECs), a small population (3‰) of HIV-infected patients with undetectable HIV replication. For that purpose, we investigated the in vitro antiviral activity of fresh CD8+ T-cells on HIV-infected CD4+ T-cells taken from 10 ECs. The 10 ECs had a classical genomic profile: all of them carried the KIR3DL1 gene and 9 carried at least 1 allele of HLA-B:Bw4-80Ile (i.e., with an isoleucine residue at position 80). In the nine HLA-B:Bw4-80Ile-positive patients, we demonstrated a strong viral suppression by KIR3DL1-expressing CD8+ T-cells that required cell-to-cell contact to switch off the activation signals in infected CD4+ T-cells. KIR3DL1-expressing CD8+ T-cells withdrawal and KIR3DL1 neutralization by a specific anti-killer cell immunoglobulin-like receptor (KIR) antibody inhibited the suppression of viral replication. Our findings provide the first evidence for an instrumental role of KIR-expressing CD8+ regulatory T-cells in the natural control of HIV-1 infection.} }