Frontiers in Immunology (Apr 2016)

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

  • Wei eLu,
  • Wei eLu,
  • Chen eSong,
  • Chunhui eLai,
  • Jun eKang,
  • Hua eFang,
  • Hong eDao,
  • Mingyue eLai,
  • Jianhua eFan,
  • Weizhong eGuo,
  • Linchun eFu,
  • Jean Marie eAndrieu

DOI
https://doi.org/10.3389/fimmu.2016.00134
Journal volume & issue
Vol. 7

Abstract

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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.

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