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HIV-1-Specific CD11c⁺ CD8⁺ T Cells Display Low PD-1 Expression and Strong Anti-HIV-1 Activity.

ABSTRACT: Exhaustion of HIV-1-specific CD8⁺ T cells prevents optimal control of HIV-1 infection. Identifying unconventional CD8⁺ T cell subsets to effectively control HIV-1 replication is vital. In this study, the role of CD11c⁺ CD8⁺ T cells during HIV-1 infection was evaluated. The frequencies of CD11c⁺ CD8⁺ T cells significantly increased and were negatively correlated with viral load in HIV-1-infected treatment-naïve patients. HIV-1-specific cells were enriched more in CD11c⁺ CD8⁺ T cells than in CD11c^- CD8⁺ T cells, which could be induced by HIV-1-derived overlapping peptides, marking an HIV-1-specific CD8⁺ T cell population. This subset expressed higher levels of activating markers (CD38 and HLA-DR), cytotoxic markers (granzyme B, perforin, and CD107a), and cytokines (IL-2 and TNF-α), with lower levels of PD-1 compared to the CD11c^- CD8⁺ T cell subset. In vitro analysis verified that CD11c⁺ CD8⁺ T cells displayed a stronger HIV-1-specific killing capacity than the CD11c^- counterparts. These findings indicate that CD11c⁺ CD8⁺ T cells have potent immunotherapeutic efficacy in controlling HIV-1 infection.

SUBMITTER: Guo AL

PROVIDER: S-EPMC8554207 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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HIV-1-Specific CD11c+ CD8+ T Cells Display Low PD-1 Expression and Strong Anti-HIV-1 Activity.

Guo An-Liang AL Zhao Jin-Fang JF Gao Lin L Huang Hui-Huang HH Zhang Ji-Yuan JY Zhang Chao C Song Jin-Wen JW Xu Ruo-Nan RN Fan Xing X Shi Ming M Jiao Yan-Mei YM Wang Fu-Sheng FS

Frontiers in immunology 20211015

Exhaustion of HIV-1-specific CD8+ T cells prevents optimal control of HIV-1 infection. Identifying unconventional CD8+ T cell subsets to effectively control HIV-1 replication is vital. In this study, the role of CD11c+ CD8+ T cells during HIV-1 infection was evaluated. The frequencies of CD11c+ CD8+ T cells significantly increased and were negatively correlated with viral load in HIV-1-infected treatment-naïve patients. HIV-1-spec ...[more]

PMID: 34721433

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Project description:BackgroundDevelopment of AIDS vaccines for effective prevention of circulating HIV-1 is required, but no trial has demonstrated definitive effects on the prevention. Several recent T-cell vaccine trials showed no protection against HIV-1 acquisition although the vaccines induced HIV-1-specific T-cell responses, suggesting that the vaccine-induced T cells have insufficient capacities to suppress HIV-1 replication and/or cross-recognize circulating HIV-1. Therefore, it is necessary to develop T-cell vaccines that elicit T cells recognizing shared protective epitopes with strong ability to suppress HIV-1. We recently designed T-cell mosaic vaccine immunogens tHIVconsvX composed of 6 conserved Gag and Pol regions and demonstrated that the T-cell responses to peptides derived from the vaccine immunogens were significantly associated with lower plasma viral load (pVL) and higher CD4+ T-cell count (CD4 count) in HIV-1-infected, treatment-naive Japanese individuals. However, it remains unknown T cells of which specificities have the ability to suppress HIV-1 replication. In the present study, we sought to identify more T cells specific for protective Gag epitopes in the vaccine immunogens, and analyze their abilities to suppress HIV-1 replication and recognize epitope variants in circulating HIV-1.ResultsWe determined 17 optimal Gag epitopes and their HLA restriction, and found that T-cell responses to 9 were associated significantly with lower pVL and/or higher CD4 count. T-cells recognizing 5 of these Gag peptides remained associated with good clinical outcome in 221 HIV-1-infected individuals even when comparing responders and non-responders with the same restricting HLA alleles. Although it was known previously that T cells specific for 3 of these protective epitopes had strong abilities to suppress HIV-1 replication in vivo, here we demonstrated equivalent abilities for the 2 novel epitopes. Furthermore, T cells against all 5 Gag epitopes cross-recognized variants in majority of circulating HIV-1.ConclusionsWe demonstrated that T cells specific for 5 Gag conserved epitopes in the tHIVconsvX have ability to suppress replication of circulating HIV-1 in HIV-1-infected individuals. Therefore, the tHIVconsvX vaccines have the right specificity to contribute to prevention of HIV-1 infection and eradication of latently infected cells following HIV-1 reactivation.

Dataset Information

HIV-1-Specific CD11c⁺ CD8⁺ T Cells Display Low PD-1 Expression and Strong Anti-HIV-1 Activity.

Publications

HIV-1-Specific CD11c<sup>+</sup> CD8<sup>+</sup> T Cells Display Low PD-1 Expression and Strong Anti-HIV-1 Activity.

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