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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

Functional features of CD8+ T-cell-mediated viral suppression. (A) CD8+ T-cell-mediated viral suppression (green) was reduced by nearly 3 logs when freshly purified CD8+ T cells were added 48 h after SEB and anti-CD3/28 stimulation (red). (B) CD8+ T-cell-mediated viral suppression (green) was reduced by 2.5 logs when CD8+ T cells were separated in a transwell culture (red). (C) No cytotoxicity was observed in autologous HIV-1-infected CD4+ T cells (target cells) co-incubated with CD8+ T-cells (effector cells) from ECs No. 1–5.
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Figure 3: Functional features of CD8+ T-cell-mediated viral suppression. (A) CD8+ T-cell-mediated viral suppression (green) was reduced by nearly 3 logs when freshly purified CD8+ T cells were added 48 h after SEB and anti-CD3/28 stimulation (red). (B) CD8+ T-cell-mediated viral suppression (green) was reduced by 2.5 logs when CD8+ T cells were separated in a transwell culture (red). (C) No cytotoxicity was observed in autologous HIV-1-infected CD4+ T cells (target cells) co-incubated with CD8+ T-cells (effector cells) from ECs No. 1–5.

Mentions: When freshly purified CD8+ T-cells (stimulated at the same time as target CD4+ T-cells with SEB and anti-CD3/anti-CD28 antibodies) were added 48 h after the activation of HIV-1-superinfected CD4+ T-cells, viral suppression was much less effective (<3 logs) compared to that obtained when CD8+ T-cells were added before T-cell activation where viral suppression was maximum (>5 logs) (P < 0.05) (Figure 3A). This observation indicates that the inhibition of viral replication by CD8+ T-cells is more efficient when CD4+ T-cells are quiescent/not activated.


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)

Functional features of CD8+ T-cell-mediated viral suppression. (A) CD8+ T-cell-mediated viral suppression (green) was reduced by nearly 3 logs when freshly purified CD8+ T cells were added 48 h after SEB and anti-CD3/28 stimulation (red). (B) CD8+ T-cell-mediated viral suppression (green) was reduced by 2.5 logs when CD8+ T cells were separated in a transwell culture (red). (C) No cytotoxicity was observed in autologous HIV-1-infected CD4+ T cells (target cells) co-incubated with CD8+ T-cells (effector cells) from ECs No. 1–5.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Functional features of CD8+ T-cell-mediated viral suppression. (A) CD8+ T-cell-mediated viral suppression (green) was reduced by nearly 3 logs when freshly purified CD8+ T cells were added 48 h after SEB and anti-CD3/28 stimulation (red). (B) CD8+ T-cell-mediated viral suppression (green) was reduced by 2.5 logs when CD8+ T cells were separated in a transwell culture (red). (C) No cytotoxicity was observed in autologous HIV-1-infected CD4+ T cells (target cells) co-incubated with CD8+ T-cells (effector cells) from ECs No. 1–5.
Mentions: When freshly purified CD8+ T-cells (stimulated at the same time as target CD4+ T-cells with SEB and anti-CD3/anti-CD28 antibodies) were added 48 h after the activation of HIV-1-superinfected CD4+ T-cells, viral suppression was much less effective (<3 logs) compared to that obtained when CD8+ T-cells were added before T-cell activation where viral suppression was maximum (>5 logs) (P < 0.05) (Figure 3A). This observation indicates that the inhibition of viral replication by CD8+ T-cells is more efficient when CD4+ T-cells are quiescent/not activated.

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