Suppression of HIV replication by CD8+regulatory T-cells in elite controllers

• Main Authors: Wei eLu, Chen eSong, Chunhui eLai, Jun eKang, Hua eFang, Hong eDao, Mingyue eLai, Jianhua eFan, Weizhong eGuo, Linchun eFu, Jean Marie eAndrieu
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2016-04-01
• Series: Frontiers in Immunology
• Subjects: HIV replication; Key-words: elite controllers; suppressive/tolerogenic CD8+T-cells; CD8+ regulatory T-cells; HLA-B:Bw4-80Ile-expressing CD4+T-cells; KIR3DL1-expressing CD8+T-cells
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00134/full

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 nine carried at least one 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 byKIR3DL1-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-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.