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Initiation of Antiretroviral Therapy (ART) at Different Stages of HIV-1 Disease Is Not Associated with the Proportion of Exhausted CD8+ T Cells.

Jensen SS, Fomsgaard A, Larsen TK, Tingstedt JL, Gerstoft J, Kronborg G, Pedersen C, Karlsson I - PLoS ONE (2015)

Bottom Line: Early initiation of antiretroviral treatment (ART) and the duration of ART have been associated with immune reconstitution.The frequency of CD8+ T cells expressing the inhibitory markers PD-1, 2B4 and CD160 was lower in ART-treated individuals compared with ART-naïve individuals and similar to the frequency in HIV-uninfected controls.The expression of the three markers was similarly independent of when therapy was initiated.

View Article: PubMed Central - PubMed

Affiliation: Virus Research & Development Laboratory, Department of Microbial Diagnostic and Virology, Statens Serum Institut, Copenhagen, Denmark; Department of Infectious Diseases, Odense University Hospital, Odense, Denmark; Infectious Disease Research Unit, Clinical Institute, University of Southern Denmark, Odense, Denmark.

ABSTRACT
CD8+ T cell-restricted immunity is important in the control of HIV-1 infection, but continued immune activation results in CD8+ T cell dysfunction. Early initiation of antiretroviral treatment (ART) and the duration of ART have been associated with immune reconstitution. Here, we evaluated whether restoration of CD8+ T cell function in HIV-1-infected individuals was dependent on early initiation of ART. HIV-specific CD107a, IFNγ, IL-2, TNFα and MIP-1β expression by CD8+ T cells and the frequency of CD8+ T cells expressing PD-1, 2B4 and CD160 were measured by flow cytometry. The frequency of CD8+ T cells expressing the inhibitory markers PD-1, 2B4 and CD160 was lower in ART-treated individuals compared with ART-naïve individuals and similar to the frequency in HIV-uninfected controls. The expression of the three markers was similarly independent of when therapy was initiated. Individuals treated before seroconversion displayed an HIV-specific CD8+ T cell response that included all five functional markers; this was not observed in individuals treated after seroconversion or in ART-naïve individuals. In summary, ART appears to restore the total CD8+ T cell population to a less exhausted phenotype, independent of the time point of initiation. However, to preserve multifunctional, HIV-1-specific CD8+ T cells, ART might have to be initiated before seroconversion.

No MeSH data available.


Related in: MedlinePlus

Co-expression of PD-1, 2B4 and CD160 is independent of when ART is initiated.Co-expression of PD-1 and 2B4 or of PD-1, 2B4 and CD160 was tested in ART-naïve, ART-treated and HIV-negative individuals. A) The frequency of CD8+ T cells co-expressing PD-1 and 2B4 was significantly higher in ART-naïve individuals compared with individuals receiving ART, independent of when ART was initiated. B) The frequency of CD8+ T cells co-expressing PD-1, 2B4 and CD160 was significantly higher in ART-naïve individuals compared with ART-treated individuals and HIV-negative individuals, independent of the time of treatment initiation. ** means 0.001<p<0.01; *** means 0.0001<p<0.001 and; **** means p<0.0001.
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pone.0139573.g002: Co-expression of PD-1, 2B4 and CD160 is independent of when ART is initiated.Co-expression of PD-1 and 2B4 or of PD-1, 2B4 and CD160 was tested in ART-naïve, ART-treated and HIV-negative individuals. A) The frequency of CD8+ T cells co-expressing PD-1 and 2B4 was significantly higher in ART-naïve individuals compared with individuals receiving ART, independent of when ART was initiated. B) The frequency of CD8+ T cells co-expressing PD-1, 2B4 and CD160 was significantly higher in ART-naïve individuals compared with ART-treated individuals and HIV-negative individuals, independent of the time of treatment initiation. ** means 0.001<p<0.01; *** means 0.0001<p<0.001 and; **** means p<0.0001.

Mentions: When examining the co-expression of the inhibitory markers, the difference observed between ART-naïve and ART-treated individuals was even more pronounced. The frequency of CD8+ T cells co-expressing PD-1 and 2B4 (Fig 2A) as well as the frequency of CD8+ T cells co-expressing PD-1, 2B4 and CD160 (Fig 2B) was significantly higher in ART-naïve individuals compared with individuals receiving ART, independent of when ART was initiated. CD8+ T cells co-expressing PD-1, 2B4 and CD160 was mainly observed for CM, TM, and EM cells, and not for effectors (data not shown). The expression of these inhibitory markers was not different between individuals receiving ART and HIV-negative individuals, suggesting that ART restores the function of CD8+ T cells independent of when ART was initiated.


Initiation of Antiretroviral Therapy (ART) at Different Stages of HIV-1 Disease Is Not Associated with the Proportion of Exhausted CD8+ T Cells.

Jensen SS, Fomsgaard A, Larsen TK, Tingstedt JL, Gerstoft J, Kronborg G, Pedersen C, Karlsson I - PLoS ONE (2015)

Co-expression of PD-1, 2B4 and CD160 is independent of when ART is initiated.Co-expression of PD-1 and 2B4 or of PD-1, 2B4 and CD160 was tested in ART-naïve, ART-treated and HIV-negative individuals. A) The frequency of CD8+ T cells co-expressing PD-1 and 2B4 was significantly higher in ART-naïve individuals compared with individuals receiving ART, independent of when ART was initiated. B) The frequency of CD8+ T cells co-expressing PD-1, 2B4 and CD160 was significantly higher in ART-naïve individuals compared with ART-treated individuals and HIV-negative individuals, independent of the time of treatment initiation. ** means 0.001<p<0.01; *** means 0.0001<p<0.001 and; **** means p<0.0001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591005&req=5

pone.0139573.g002: Co-expression of PD-1, 2B4 and CD160 is independent of when ART is initiated.Co-expression of PD-1 and 2B4 or of PD-1, 2B4 and CD160 was tested in ART-naïve, ART-treated and HIV-negative individuals. A) The frequency of CD8+ T cells co-expressing PD-1 and 2B4 was significantly higher in ART-naïve individuals compared with individuals receiving ART, independent of when ART was initiated. B) The frequency of CD8+ T cells co-expressing PD-1, 2B4 and CD160 was significantly higher in ART-naïve individuals compared with ART-treated individuals and HIV-negative individuals, independent of the time of treatment initiation. ** means 0.001<p<0.01; *** means 0.0001<p<0.001 and; **** means p<0.0001.
Mentions: When examining the co-expression of the inhibitory markers, the difference observed between ART-naïve and ART-treated individuals was even more pronounced. The frequency of CD8+ T cells co-expressing PD-1 and 2B4 (Fig 2A) as well as the frequency of CD8+ T cells co-expressing PD-1, 2B4 and CD160 (Fig 2B) was significantly higher in ART-naïve individuals compared with individuals receiving ART, independent of when ART was initiated. CD8+ T cells co-expressing PD-1, 2B4 and CD160 was mainly observed for CM, TM, and EM cells, and not for effectors (data not shown). The expression of these inhibitory markers was not different between individuals receiving ART and HIV-negative individuals, suggesting that ART restores the function of CD8+ T cells independent of when ART was initiated.

Bottom Line: Early initiation of antiretroviral treatment (ART) and the duration of ART have been associated with immune reconstitution.The frequency of CD8+ T cells expressing the inhibitory markers PD-1, 2B4 and CD160 was lower in ART-treated individuals compared with ART-naïve individuals and similar to the frequency in HIV-uninfected controls.The expression of the three markers was similarly independent of when therapy was initiated.

View Article: PubMed Central - PubMed

Affiliation: Virus Research & Development Laboratory, Department of Microbial Diagnostic and Virology, Statens Serum Institut, Copenhagen, Denmark; Department of Infectious Diseases, Odense University Hospital, Odense, Denmark; Infectious Disease Research Unit, Clinical Institute, University of Southern Denmark, Odense, Denmark.

ABSTRACT
CD8+ T cell-restricted immunity is important in the control of HIV-1 infection, but continued immune activation results in CD8+ T cell dysfunction. Early initiation of antiretroviral treatment (ART) and the duration of ART have been associated with immune reconstitution. Here, we evaluated whether restoration of CD8+ T cell function in HIV-1-infected individuals was dependent on early initiation of ART. HIV-specific CD107a, IFNγ, IL-2, TNFα and MIP-1β expression by CD8+ T cells and the frequency of CD8+ T cells expressing PD-1, 2B4 and CD160 were measured by flow cytometry. The frequency of CD8+ T cells expressing the inhibitory markers PD-1, 2B4 and CD160 was lower in ART-treated individuals compared with ART-naïve individuals and similar to the frequency in HIV-uninfected controls. The expression of the three markers was similarly independent of when therapy was initiated. Individuals treated before seroconversion displayed an HIV-specific CD8+ T cell response that included all five functional markers; this was not observed in individuals treated after seroconversion or in ART-naïve individuals. In summary, ART appears to restore the total CD8+ T cell population to a less exhausted phenotype, independent of the time point of initiation. However, to preserve multifunctional, HIV-1-specific CD8+ T cells, ART might have to be initiated before seroconversion.

No MeSH data available.


Related in: MedlinePlus