title: Suppression of HIV Replication by CD8(+) Regulatory T-Cells in Elite Controllers.
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.
authors.affiliation: Institut de Recherche sur les Vaccins et l'Immunothérapie des Cancers et du Sida, Université de Paris Descartes, Paris, France; Sino-French Collaborative Laboratory, Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Sino-French Collaborative Laboratory, Tropical Medicine Institute, Guangzhou University of Chinese Medicine , Guangzhou , China.
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.affiliation: Sino-French Collaborative Laboratory, Tropical Medicine Institute, Guangzhou University of Chinese Medicine , Guangzhou , China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Lai
authors.affiliation: Xishuangbanna Center for Disease Control and Prevention , Jinghong , China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Lai
authors.affiliation: Xishuangbanna Center for Disease Control and Prevention , Jinghong , China.
authors.forename: Hua
authors.initials: H
authors.lastname: Fang
authors.affiliation: Xishuangbanna Center for Disease Control and Prevention , Jinghong , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Dao
authors.affiliation: Xishuangbanna Center for Disease Control and Prevention , Jinghong , China.
authors.forename: Jun
authors.initials: J
authors.lastname: Kang
authors.affiliation: Xishuangbanna Center for Disease Control and Prevention , Jinghong , China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Fan
authors.affiliation: Sino-French Collaborative Laboratory, Tropical Medicine Institute, Guangzhou University of Chinese Medicine , Guangzhou , China.
authors.forename: Weizhong
authors.initials: W
authors.lastname: Guo
authors.affiliation: Sino-French Collaborative Laboratory, Tropical Medicine Institute, Guangzhou University of Chinese Medicine , Guangzhou , China.
authors.forename: Linchun
authors.initials: L
authors.lastname: Fu
authors.affiliation: Institut de Recherche sur les Vaccins et l'Immunothérapie des Cancers et du Sida, Université de Paris Descartes , Paris , France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Andrieu
keywords: AIDS; CD4+ T-cells; HIV-1 suppression assay; HLA-B:Bw4-80Ile gene; KIR3DL1-expressing CD8+ T-cells; NK cells; elite controllers; suppressive/regulatory CD8+ T-cells