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

TY - JOUR

T1 - Initiation of Antiretroviral Therapy (ART) at Different Stages of HIV-1 Disease Is Not Associated with the Proportion of Exhausted CD8+ T Cells

AU - Jensen, Sanne Skov

AU - Fomsgaard, Anders

AU - Larsen, Tine Kochendorf

AU - Tingstedt, Jeanette Linnea

AU - Gerstoft, Jan

AU - Kronborg, Gitte

AU - Pedersen, Court

AU - Karlsson, Ingrid

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0139573

DO - 10.1371/journal.pone.0139573

M3 - Journal article

C2 - 26426913

SN - 1932-6203

VL - 10

SP - 1

EP - 14

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 10

M1 - e0139573

ER -