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Peripheral Vγ9Vδ2 T Cells Are a Novel Reservoir of Latent HIV Infection.

Soriano-Sarabia N, Archin NM, Bateson R, Dahl NP, Crooks AM, Kuruc JD, Garrido C, Margolis DM - PLoS Pathog. (2015)

Bottom Line: Eradication of HIV infection will require the identification of all cellular reservoirs that harbor latent infection.We found that upregulation of the CD4 receptor may render primary Vδ2 cells target for HIV infection in vitro and we propose that HIV-induced immune activation may allow infection of γδ T cells in vivo.In 14 patients we recovered latent but replication-competent HIV from highly purified Vδ2 cells demonstrating that peripheral Vδ2 T cells are a previously unrecognized reservoir in which latent HIV infection is unexpectedly frequent.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.

ABSTRACT
Eradication of HIV infection will require the identification of all cellular reservoirs that harbor latent infection. Despite low or lack of CD4 receptor expression on Vδ2 T cells, infection of these cells has previously been reported. We found that upregulation of the CD4 receptor may render primary Vδ2 cells target for HIV infection in vitro and we propose that HIV-induced immune activation may allow infection of γδ T cells in vivo. We assessed the presence of latent HIV infection by measurements of DNA and outgrowth assays within Vδ2 cells in 18 aviremic patients on long-standing antiretroviral therapy. In 14 patients we recovered latent but replication-competent HIV from highly purified Vδ2 cells demonstrating that peripheral Vδ2 T cells are a previously unrecognized reservoir in which latent HIV infection is unexpectedly frequent.

No MeSH data available.


Related in: MedlinePlus

Vδ2 cells exhibit potent anti-HIV activity in vitro.Isolated Vδ2 cells from healthy donors were co-cultured with autologous in vitro infected HIV- CD4+ T cells at 1:0.1 or 1:0.01 ratios (CD4:Vδ2) for seven days. HIV p24 production was inhibited in a cell-dose-dependent manner. When a cocktail of blocking antibodies against CD8, CD16 and NKG2D were added, cytotoxic function of Vδ2 cells was partially abrogated. Mean±SE of three different donors is represented.
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ppat.1005201.g005: Vδ2 cells exhibit potent anti-HIV activity in vitro.Isolated Vδ2 cells from healthy donors were co-cultured with autologous in vitro infected HIV- CD4+ T cells at 1:0.1 or 1:0.01 ratios (CD4:Vδ2) for seven days. HIV p24 production was inhibited in a cell-dose-dependent manner. When a cocktail of blocking antibodies against CD8, CD16 and NKG2D were added, cytotoxic function of Vδ2 cells was partially abrogated. Mean±SE of three different donors is represented.

Mentions: Interestingly, while quantifying the frequency of infection within Vδ2 cells by limiting dilution assay, in some patients we found an unusual pattern of recovery of HIV with more positive wells at lower dilutions and no virus recovered when more cells were cultured (Fig 3). As γδ T cells possess innate, nonspecific antiviral function [25,26], we hypothesized that an antiviral activity of the uninfected γδ T cells might reduce the recovery of HIV in cultures with high cell inputs, yielding the unusual pattern of viral outgrowth seen in some patients. To test this hypothesis, we performed viral inhibition assays, co-culturing Vδ2 cells from a healthy, uninfected donor, with autologous CD4+ T cells that had been HIV-infected ex vivo at ratios of 1 CD4 cell and 0.1 or 0.01 γδ cells. Vδ2 T cells inhibited HIV production from infected CD4+ T cells, with increased inhibition seen at higher cell inputs in the co-culture system (Fig 5). In addition, in some wells we blocked the cytotoxic activity of γδ T cells by pre-incubating the isolated Vδ2 cells with a cocktail of antibodies against CD8, NKG2D and CD16 (Fig 5). HIV p24 production was 74.6% inhibited in the 1:0.1 ratio conditions and 41.8% in the 1:0.01 conditions. When the cocktail of antibodies was used, these percentages decreased to 26.9% and 15.5% in the 1:0.1 and 1:0.01 ratios, respectively.


Peripheral Vγ9Vδ2 T Cells Are a Novel Reservoir of Latent HIV Infection.

Soriano-Sarabia N, Archin NM, Bateson R, Dahl NP, Crooks AM, Kuruc JD, Garrido C, Margolis DM - PLoS Pathog. (2015)

Vδ2 cells exhibit potent anti-HIV activity in vitro.Isolated Vδ2 cells from healthy donors were co-cultured with autologous in vitro infected HIV- CD4+ T cells at 1:0.1 or 1:0.01 ratios (CD4:Vδ2) for seven days. HIV p24 production was inhibited in a cell-dose-dependent manner. When a cocktail of blocking antibodies against CD8, CD16 and NKG2D were added, cytotoxic function of Vδ2 cells was partially abrogated. Mean±SE of three different donors is represented.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608739&req=5

ppat.1005201.g005: Vδ2 cells exhibit potent anti-HIV activity in vitro.Isolated Vδ2 cells from healthy donors were co-cultured with autologous in vitro infected HIV- CD4+ T cells at 1:0.1 or 1:0.01 ratios (CD4:Vδ2) for seven days. HIV p24 production was inhibited in a cell-dose-dependent manner. When a cocktail of blocking antibodies against CD8, CD16 and NKG2D were added, cytotoxic function of Vδ2 cells was partially abrogated. Mean±SE of three different donors is represented.
Mentions: Interestingly, while quantifying the frequency of infection within Vδ2 cells by limiting dilution assay, in some patients we found an unusual pattern of recovery of HIV with more positive wells at lower dilutions and no virus recovered when more cells were cultured (Fig 3). As γδ T cells possess innate, nonspecific antiviral function [25,26], we hypothesized that an antiviral activity of the uninfected γδ T cells might reduce the recovery of HIV in cultures with high cell inputs, yielding the unusual pattern of viral outgrowth seen in some patients. To test this hypothesis, we performed viral inhibition assays, co-culturing Vδ2 cells from a healthy, uninfected donor, with autologous CD4+ T cells that had been HIV-infected ex vivo at ratios of 1 CD4 cell and 0.1 or 0.01 γδ cells. Vδ2 T cells inhibited HIV production from infected CD4+ T cells, with increased inhibition seen at higher cell inputs in the co-culture system (Fig 5). In addition, in some wells we blocked the cytotoxic activity of γδ T cells by pre-incubating the isolated Vδ2 cells with a cocktail of antibodies against CD8, NKG2D and CD16 (Fig 5). HIV p24 production was 74.6% inhibited in the 1:0.1 ratio conditions and 41.8% in the 1:0.01 conditions. When the cocktail of antibodies was used, these percentages decreased to 26.9% and 15.5% in the 1:0.1 and 1:0.01 ratios, respectively.

Bottom Line: Eradication of HIV infection will require the identification of all cellular reservoirs that harbor latent infection.We found that upregulation of the CD4 receptor may render primary Vδ2 cells target for HIV infection in vitro and we propose that HIV-induced immune activation may allow infection of γδ T cells in vivo.In 14 patients we recovered latent but replication-competent HIV from highly purified Vδ2 cells demonstrating that peripheral Vδ2 T cells are a previously unrecognized reservoir in which latent HIV infection is unexpectedly frequent.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.

ABSTRACT
Eradication of HIV infection will require the identification of all cellular reservoirs that harbor latent infection. Despite low or lack of CD4 receptor expression on Vδ2 T cells, infection of these cells has previously been reported. We found that upregulation of the CD4 receptor may render primary Vδ2 cells target for HIV infection in vitro and we propose that HIV-induced immune activation may allow infection of γδ T cells in vivo. We assessed the presence of latent HIV infection by measurements of DNA and outgrowth assays within Vδ2 cells in 18 aviremic patients on long-standing antiretroviral therapy. In 14 patients we recovered latent but replication-competent HIV from highly purified Vδ2 cells demonstrating that peripheral Vδ2 T cells are a previously unrecognized reservoir in which latent HIV infection is unexpectedly frequent.

No MeSH data available.


Related in: MedlinePlus