AUTHOR=Lu Wei , Chen Song , Lai Chunhui , Lai Mingyue , Fang Hua , Dao Hong , Kang Jun , Fan Jianhua , Guo Weizhong , Fu Linchun , Andrieu Jean-Marie 

TITLE=Suppression of HIV Replication by CD8+ Regulatory T-Cells in Elite Controllers

JOURNAL=Frontiers in Immunology

VOLUME=Volume 7 - 2016

YEAR=2016

URL=https://www.frontiersin.org/journals/immunology/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  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 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-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.