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Combination Immune Checkpoint Blockade Enhances IL-2 and CD107a Production from HIV-Specific T Cells Ex Vivo in People Living with HIV on Antiretroviral Therapy.

ABSTRACT: In people with HIV (PWH) on antiretroviral therapy (ART), immune dysfunction persists, including elevated expression of immune checkpoint (IC) proteins on total and HIV-specific T cells. Reversing immune exhaustion is one strategy to enhance the elimination of HIV-infected cells that persist in PWH on ART. We aimed to evaluate whether blocking CTL-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), T cell Ig domain and mucin domain 3 (TIM-3), T cell Ig and ITIM domain (TIGIT) and lymphocyte activation gene-3 (LAG-3) alone or in combination would enhance HIV-specific CD4⁺ and CD8⁺ T cell function ex vivo. Intracellular cytokine staining was performed using human PBMCs from PWH on ART (n = 11) and expression of CD107a, IFN-γ, TNF-α, and IL-2 was quantified with HIV peptides and Abs to IC. We found the following: 1) IC blockade enhanced the induction of CD107a and IL-2 but not IFN-γ and TNF-α in response to Gag and Nef peptides; 2) the induction of CD107a and IL-2 was greatest with multiple combinations of two Abs; and 3) Abs to LAG-3, CTLA-4, and TIGIT in combinations showed synergistic induction of IL-2 in HIV-specific CD8⁺ and CD107a and IL-2 production in HIV-specific CD4⁺ and CD8⁺ T cells. These results demonstrate that the combination of Abs to LAG-3, CTLA-4, or TIGIT can increase the frequency of cells expressing CD107a and IL-2 that associated with cytotoxicity and survival of HIV-specific CD4⁺ and CD8⁺ T cells in PWH on ART. These combinations should be further explored for an HIV cure.

SUBMITTER: Chiu CY

PROVIDER: S-EPMC8702486 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Combination Immune Checkpoint Blockade Enhances IL-2 and CD107a Production from HIV-Specific T Cells Ex Vivo in People Living with HIV on Antiretroviral Therapy.

Chiu Chris Y CY Chang Judy J JJ Dantanarayana Ashanti I AI Solomon Ajantha A Evans Vanessa A VA Pascoe Rachel R Gubser Céline C Trautman Lydie L Fromentin Rémi R Chomont Nicolas N McMahon James H JH Cameron Paul U PU Rasmussen Thomas A TA Lewin Sharon R SR

Journal of immunology (Baltimore, Md. : 1950) 20211201 1

In people with HIV (PWH) on antiretroviral therapy (ART), immune dysfunction persists, including elevated expression of immune checkpoint (IC) proteins on total and HIV-specific T cells. Reversing immune exhaustion is one strategy to enhance the elimination of HIV-infected cells that persist in PWH on ART. We aimed to evaluate whether blocking CTL-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), T cell Ig domain and mucin domain 3 (TIM-3), T cell Ig and ITIM domain (TIGIT) ...[more]

PMID: 34853078

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Project description:BackgroundWith the ageing of people living with HIV/AIDS (PLWHA), the prevalence of chronic comorbidities, especially hyperglycaemia, is increasing among elderly PLWHA. Antiretroviral therapy (ART) is associated with fasting plasma glucose (FPG) levels. This study aimed to investigate both short-term and long-term FPG characteristics and trends across different ART regimens in elderly Chinese PLWHA.MethodsThis retrospective cohort study, based on hospital treatment information, classified ART regimens as this retrospective cohort study used hospital treatment data. ART regimens are classified into three categories: non-nucleoside reverse transcriptase inhibitors (NNRTIs) based, protease inhibitors (PIs) based and integrase strand transfer inhibitor (INSTIs) based. Propensity score matching was applied to control for confounding factors. Follow-up FPG characteristics were then described, and a generalised linear mixed model was employed to estimate FPG trends under different regimens within 1-year and 5-year periods following ART initiation.ResultsParticipants had an average age of 58.28 years, with 75.02% male. FPG increased following ART initiation, with the most significant rise within 1 year of ART, followed by stabilisation. The FPG increase within 1 year was slower in the PIs-based group compared with the NNRTIs-based group (β=-0.08, 95% CI -0.15 to -0.01), while there was a higher prevalence of diabetes within 5 years of ART (31.55% vs 22.33%, standardised difference=0.357). The FPG increase within 1 year of ART did not differ between NNRTIs-based and INSTIs-based groups (β=-0.01, 95% CI -0.20, 0.18).ConclusionOur study highlights that elderly Chinese PLWHA experience an increase in FPG levels, particularly during the first year of ART, with variations observed across different ART regimens. The higher long-term prevalence of diabetes in the PIs-based regimen group emphasises the need for tailored glucose management strategies. Routine glucose monitoring and proactive management are crucial for preventing and controlling diabetes in this population, particularly given the long-term metabolic risks associated with ART.

Dataset Information

Combination Immune Checkpoint Blockade Enhances IL-2 and CD107a Production from HIV-Specific T Cells Ex Vivo in People Living with HIV on Antiretroviral Therapy.

Publications

Combination Immune Checkpoint Blockade Enhances IL-2 and CD107a Production from HIV-Specific T Cells Ex Vivo in People Living with HIV on Antiretroviral Therapy.

Similar Datasets

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