HIV-Specific CD8+ T Cell-Mediated Viral Suppression Correlates With the Expression of CD57

TY - JOUR

T1 - HIV-Specific CD8+ T Cell-Mediated Viral Suppression Correlates With the Expression of CD57

AU - Jensen, Sanne S

AU - Tingstedt, Jeanette Linnea

AU - Larsen, Tine Kochendorf

AU - Brandt, Lea

AU - Gerstoft, Jan

AU - Kronborg, Gitte

AU - Pedersen, Court

AU - Fomsgaard, Anders

AU - Karlsson, Ingrid

PY - 2016/1/1

Y1 - 2016/1/1

N2 - BACKGROUND: Virus-specific CD8(+) T-cell responses are believed to play an important role in the control of HIV-1 infection; however, what constitutes an effective HIV-1 CD8(+) T-cell response remains a topic of debate. The ex vivo viral suppressive capacity was measured of CD8(+) T cells from 44 HIV-1-positive individuals. The phenotypic and cytokine profiles, and also the specificity of the CD8(+) T cells, were correlated with the suppression of HIV-1 replication. We also aimed to determine whether antiretroviral therapy (ART) had any positive effect on the HIV-1 suppressive CD8(+) T cells.METHOD: Ex vivo suppression assay was used to evaluate the ability of CD8(+) T cells to suppress HIV-1 replication in autologous CD4(+) T cells. The CD107a, interferon-γ, interleukin-2, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein-1β (MIP-1β) responses to HIV-1 were evaluated by intracellular staining. The phenotypic profile of CD8(+) T cells was determined by whole blood staining.RESULTS: The expression of CD57 on effector CD8(+) T cells correlated with the suppression of HIV-1 replication and to the duration of ART. CD107a and tumor necrosis factor-α expression levels were significantly higher in individuals with ex vivo suppressive activity compared with individuals without suppressive activity.CONCLUSIONS: Standard in vitro assays measuring one or several cytokines do not correlate with the functional viral suppressive capacity of CD8(+) T cells from HIV-1-positive individuals. The best correlation of viral suppression was found to be CD57 expression. CD57 expression correlated with the duration of ART, suggesting that ART restores the cytotoxic capacity of CD8(+) T lymphocytes.

AB - BACKGROUND: Virus-specific CD8(+) T-cell responses are believed to play an important role in the control of HIV-1 infection; however, what constitutes an effective HIV-1 CD8(+) T-cell response remains a topic of debate. The ex vivo viral suppressive capacity was measured of CD8(+) T cells from 44 HIV-1-positive individuals. The phenotypic and cytokine profiles, and also the specificity of the CD8(+) T cells, were correlated with the suppression of HIV-1 replication. We also aimed to determine whether antiretroviral therapy (ART) had any positive effect on the HIV-1 suppressive CD8(+) T cells.METHOD: Ex vivo suppression assay was used to evaluate the ability of CD8(+) T cells to suppress HIV-1 replication in autologous CD4(+) T cells. The CD107a, interferon-γ, interleukin-2, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein-1β (MIP-1β) responses to HIV-1 were evaluated by intracellular staining. The phenotypic profile of CD8(+) T cells was determined by whole blood staining.RESULTS: The expression of CD57 on effector CD8(+) T cells correlated with the suppression of HIV-1 replication and to the duration of ART. CD107a and tumor necrosis factor-α expression levels were significantly higher in individuals with ex vivo suppressive activity compared with individuals without suppressive activity.CONCLUSIONS: Standard in vitro assays measuring one or several cytokines do not correlate with the functional viral suppressive capacity of CD8(+) T cells from HIV-1-positive individuals. The best correlation of viral suppression was found to be CD57 expression. CD57 expression correlated with the duration of ART, suggesting that ART restores the cytotoxic capacity of CD8(+) T lymphocytes.

U2 - 10.1097/QAI.0000000000000837

DO - 10.1097/QAI.0000000000000837

M3 - Journal article

C2 - 26761268

SN - 1525-4135

VL - 71

SP - 8

EP - 16

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

IS - 1

ER -