Functional and transcriptional senescence profiles of CD8+ T cells associate with the presence of carotid plaques in people living with HIV.
단면연구
1/5 보강
PICO 자동 추출 (휴리스틱, conf 3/4)
유사 논문P · Population 대상 환자/모집단
584 participants (49%) - 502 of 994 (51%) in the discovery and 82 of 200 (41%) in the validation cohort.
I · Intervention 중재 / 시술
carotid ultrasound imaging to assess plaques using standardized criteria
C · Comparison 대조 / 비교
추출되지 않음
O · Outcome 결과 / 결론
Targeting immune senescence could offer a novel strategy for cardiovascular risk reduction in this population. [TRIAL REGISTRATION] ClinicalTrials.gov Identifier: NCT03994835.
[BACKGROUND] People living with HIV (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD), but the immunological mechanisms driving plaque formation remain unclear.
- 표본수 (n) 994
- 연구 설계 cross-sectional
APA
Blaauw MJT, Navas A, et al. (2026). Functional and transcriptional senescence profiles of CD8+ T cells associate with the presence of carotid plaques in people living with HIV.. The Journal of infectious diseases. https://doi.org/10.1093/infdis/jiag018
MLA
Blaauw MJT, et al.. "Functional and transcriptional senescence profiles of CD8+ T cells associate with the presence of carotid plaques in people living with HIV.." The Journal of infectious diseases, 2026.
PMID
41498526
Abstract
[BACKGROUND] People living with HIV (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD), but the immunological mechanisms driving plaque formation remain unclear. This study investigated the association between peripheral immune cell subsets and carotid atherosclerotic plaques in PLHIV without prior clinical ASCVD.
[METHODS] In this multi-center cross-sectional study, virally suppressed PLHIV receiving antiretroviral therapy were enrolled from two Dutch cohorts: a discovery cohort (n= 994) and a validation cohort (n= 200). Between November 2019 and October 2021, participants underwent carotid ultrasound imaging to assess plaques using standardized criteria. Immune profiling was performed using high-dimensional flow cytometry of 355 immune cell populations. Associations with plaque were analyzed using linear regression adjusted for relevant confounders, and key findings were validated in the second cohort. Transcriptomic profiles of main cell populations were evaluated using deconvoluted bulk RNA sequencing to identify differential expression and pathway enrichment.
[RESULTS] Carotid plaques were present in 584 participants (49%) - 502 of 994 (51%) in the discovery and 82 of 200 (41%) in the validation cohort. Plaques were associated with higher counts of several CD8+ T cell subsets, particularly PD-1-expressing cytotoxic T cells with an interferon secretion profile (CD8TC1PD1+). Transcriptomic analysis of CD8+ T cells revealed downregulated mitochondrial function and upregulated type 1 interferon and epidermal growth factor receptor (EGFR) signaling, indicating a senescent phenotype.
[CONCLUSIONS] CD8+ T cell senescence may contribute to early atherosclerotic plaque formation in PLHIV. Targeting immune senescence could offer a novel strategy for cardiovascular risk reduction in this population.
[TRIAL REGISTRATION] ClinicalTrials.gov Identifier: NCT03994835.
[METHODS] In this multi-center cross-sectional study, virally suppressed PLHIV receiving antiretroviral therapy were enrolled from two Dutch cohorts: a discovery cohort (n= 994) and a validation cohort (n= 200). Between November 2019 and October 2021, participants underwent carotid ultrasound imaging to assess plaques using standardized criteria. Immune profiling was performed using high-dimensional flow cytometry of 355 immune cell populations. Associations with plaque were analyzed using linear regression adjusted for relevant confounders, and key findings were validated in the second cohort. Transcriptomic profiles of main cell populations were evaluated using deconvoluted bulk RNA sequencing to identify differential expression and pathway enrichment.
[RESULTS] Carotid plaques were present in 584 participants (49%) - 502 of 994 (51%) in the discovery and 82 of 200 (41%) in the validation cohort. Plaques were associated with higher counts of several CD8+ T cell subsets, particularly PD-1-expressing cytotoxic T cells with an interferon secretion profile (CD8TC1PD1+). Transcriptomic analysis of CD8+ T cells revealed downregulated mitochondrial function and upregulated type 1 interferon and epidermal growth factor receptor (EGFR) signaling, indicating a senescent phenotype.
[CONCLUSIONS] CD8+ T cell senescence may contribute to early atherosclerotic plaque formation in PLHIV. Targeting immune senescence could offer a novel strategy for cardiovascular risk reduction in this population.
[TRIAL REGISTRATION] ClinicalTrials.gov Identifier: NCT03994835.