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Suppression of HIV Replication by CD8(+) Regulatory T-Cells in Elite Controllers.

Lu W, Chen S, Lai C, Lai M, Fang H, Dao H, Kang J, Fan J, Guo W, Fu L, Andrieu JM - Front Immunol (2016)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

HLA-I and KIR alleles frequencies; differences between 10 elite controllers (ECs) and 10 patients with high viral load (HVLpts). (A) Two HLA-I B and one HLA-I A alleles were more frequent in ECs (green) than in HVLpts (red); only one HLA-A allele was more frequent in HVLpts than in ECs. (B) Five KIR alleles were more frequent in ECs (green) than in HVLpts (red). *P < 0.05; **P < 0.01.
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Figure 1: HLA-I and KIR alleles frequencies; differences between 10 elite controllers (ECs) and 10 patients with high viral load (HVLpts). (A) Two HLA-I B and one HLA-I A alleles were more frequent in ECs (green) than in HVLpts (red); only one HLA-A allele was more frequent in HVLpts than in ECs. (B) Five KIR alleles were more frequent in ECs (green) than in HVLpts (red). *P < 0.05; **P < 0.01.

Mentions: Overall, three HLA alleles (HLA-B 45Thr, 80Ile, and HLA-A 97Met) were significantly more frequent in ECs than in HVLpts (P < 0.01 for HLA-B 45Thr and 80Ile; P < 0.05 for HLA-A 97Met). One HLA allele (HLA-A 152Val) was significantly less frequent in ECs than in HVLpts (P < 0.05) (Figure 1A).


Suppression of HIV Replication by CD8(+) Regulatory T-Cells in Elite Controllers.

Lu W, Chen S, Lai C, Lai M, Fang H, Dao H, Kang J, Fan J, Guo W, Fu L, Andrieu JM - Front Immunol (2016)

HLA-I and KIR alleles frequencies; differences between 10 elite controllers (ECs) and 10 patients with high viral load (HVLpts). (A) Two HLA-I B and one HLA-I A alleles were more frequent in ECs (green) than in HVLpts (red); only one HLA-A allele was more frequent in HVLpts than in ECs. (B) Five KIR alleles were more frequent in ECs (green) than in HVLpts (red). *P < 0.05; **P < 0.01.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4834299&req=5

Figure 1: HLA-I and KIR alleles frequencies; differences between 10 elite controllers (ECs) and 10 patients with high viral load (HVLpts). (A) Two HLA-I B and one HLA-I A alleles were more frequent in ECs (green) than in HVLpts (red); only one HLA-A allele was more frequent in HVLpts than in ECs. (B) Five KIR alleles were more frequent in ECs (green) than in HVLpts (red). *P < 0.05; **P < 0.01.
Mentions: Overall, three HLA alleles (HLA-B 45Thr, 80Ile, and HLA-A 97Met) were significantly more frequent in ECs than in HVLpts (P < 0.01 for HLA-B 45Thr and 80Ile; P < 0.05 for HLA-A 97Met). One HLA allele (HLA-A 152Val) was significantly less frequent in ECs than in HVLpts (P < 0.05) (Figure 1A).

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus