TY - JOUR AU - Lu, Wei AU - Chen, Song AU - Lai, Chunhui AU - Lai, Mingyue AU - Fang, Hua AU - Dao, Hong AU - Kang, Jun AU - Fan, Jianhua AU - Guo, Weizhong AU - Fu, Linchun AU - Andrieu, Jean-Marie PY - 2016 M3 - Original Research TI - Suppression of HIV Replication by CD8+ Regulatory T-Cells in Elite Controllers JO - Frontiers in Immunology UR - https://www.frontiersin.org/articles/10.3389/fimmu.2016.00134 VL - 7 SN - 1664-3224 N2 - 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. ER -