Dataset Information

Persistent CD38 Expression on CD8 + T Lymphocytes Contributes to Altered Mitochondrial Function and Chronic Inflammation in People With HIV, Despite ART.

ABSTRACT:

Background

Age-associated comorbidities are higher in people with HIV (PWH) than HIV-negative individuals. This is partially attributed to immune activation and CD38 expression on T cells driving chronic inflammation. However, the exact contribution of CD38-expressing T cells on the proinflammatory response is not completely understood.

Methods

CD38-expressing CD8 + T lymphocytes were measured from PWH and HIV-negative individuals. Mitochondrial mass, superoxide content, membrane depolarization of CD4 + and CD8 + T lymphocytes, and cytokine production after HIV(Gag)-specific peptide stimulation from CD38 + CD8 + T lymphocytes of PWH were measured to link biological effects of CD38 expression on cellular metabolism.

Results

The frequency of activated CD8 + CD38 + T cells persists in PWH on ART compared with HIV-negative individuals. Higher CD38 expression is associated with mitochondrial biogenesis and HIV(Gag)-specific proinflammatory cytokine production in PWH. Blockade of CD38 results in lower Gag-specific cytokine production.

Conclusions

ART only partially reduced HIV-induced CD38 expression on CD8 + T cells. CD8 + CD38 + T cells are highly activated in vivo, and HIV-specific stimulation in vitro augments CD38 expression, contributing to a proinflammatory response despite virologic control with ART. Therefore, CD38 is a potential therapeutic target for mitigating chronic inflammation that likely drives cellular aging, comorbidities, and end-organ disease in PWH.

SUBMITTER: Mathur P

PROVIDER: S-EPMC9613598 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Persistent CD38 Expression on CD8 + T Lymphocytes Contributes to Altered Mitochondrial Function and Chronic Inflammation in People With HIV, Despite ART.

Mathur Poonam P Kottilil Shyamasundaran S Pallikkuth Suresh S Frasca Daniela D Ghosh Alip A

Journal of acquired immune deficiency syndromes (1999) 20221201 4

<h4>Background</h4>Age-associated comorbidities are higher in people with HIV (PWH) than HIV-negative individuals. This is partially attributed to immune activation and CD38 expression on T cells driving chronic inflammation. However, the exact contribution of CD38-expressing T cells on the proinflammatory response is not completely understood.<h4>Methods</h4>CD38-expressing CD8 + T lymphocytes were measured from PWH and HIV-negative individuals. Mitochondrial mass, superoxide content, membrane ...[more]

PMID: 36000933

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Project description:Persistent bronchial dysplasia is associated with increased risk of developing invasive squamous cell carcinoma (SCC) of the lung. In this study, we hypothesized that differences in gene expression profiles between persistent and regressive bronchial dysplasia would identify cellular processes that underlie progression to SCC. RNA expression arrays comparing baseline biopsies from 32 bronchial sites that persisted/progressed to 31 regressive sites showed 395 differentially expressed genes [ANOVA, FDR ≤ 0.05). Thirty-one pathways showed significantly altered activity between the two groups, many of which were associated with cell-cycle control and proliferation, inflammation, or epithelial differentiation/cell-cell adhesion. Cultured persistent bronchial dysplasia cells exhibited increased expression of Polo-like kinase 1 (PLK1), which was associated with multiple cell-cycle pathways. Treatment with PLK1 inhibitor induced apoptosis and G2-M arrest and decreased proliferation compared with untreated cells; these effects were not seen in normal or regressive bronchial dysplasia cultures. Inflammatory pathway activity was decreased in persistent bronchial dysplasia, and the presence of an inflammatory infiltrate was more common in regressive bronchial dysplasia. Regressive bronchial dysplasia was also associated with trends toward overall increases in macrophages and T lymphocytes and altered polarization of these inflammatory cell subsets. Increased desmoglein 3 and plakoglobin expression was associated with higher grade and persistence of bronchial dysplasia. These results identify alterations in the persistent subset of bronchial dysplasia that are associated with high risk for progression to invasive SCC. These alterations may serve as strong markers of risk and as effective targets for lung cancer prevention.Significance: Gene expression profiling of high-risk persistent bronchial dysplasia reveals changes in cell-cycle control, inflammatory activity, and epithelial differentiation/cell-cell adhesion that may underlie progression to invasive SCC. Cancer Res; 78(17); 4971-83. ©2018 AACR.

Dataset Information

Persistent CD38 Expression on CD8 + T Lymphocytes Contributes to Altered Mitochondrial Function and Chronic Inflammation in People With HIV, Despite ART.

Background

Methods

Results

Conclusions

Publications

Persistent CD38 Expression on CD8 + T Lymphocytes Contributes to Altered Mitochondrial Function and Chronic Inflammation in People With HIV, Despite ART.

Similar Datasets

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