CD28-expressing δ T cells are increased in perivascular adipose tissue of hypertensive mice and in subcutaneous adipose tissue of obese humans

Abstract

Objectives: γδ T-lymphocytes play a role in angiotensin II (AngII)-induced hypertension, vascular injury and T-cell infiltration in perivascular adipose tissue (PVAT) in mice. Mesenteric arteries of hypertensive mice and subcutaneous arteries from obese humans present similar remodeling. We hypothesized that γδ T-cell subtypes in mesenteric vessels with PVAT (MV/PVAT) from hypertensive mice and subcutaneous adipose tissue (SAT) from obese humans, who are prone to develop hypertension, would be similar. Methods: Mice were infused with AngII for 14 days. MV/PVAT T-cells were used for single-cell RNA-sequencing (scRNA-seq). scRNA-seq data (GSE155960) of SAT CD45+ cells from three lean and three obese women were downloaded from the Gene Expression Omnibus database. Results: δ T-cell subclustering identified six δ T-cell subtypes. AngII increased T-cell receptor δ variable 4 (Trdv4)+ γδ T-effector memory cells and Cd28 high δ TEM-cells, changes confirmed by flow cytometry. δ T-cell subclustering identified nine δ T-cell subtypes in human SAT. CD28 expressing δ T-cell subclustering demonstrated similar δ T-cell subpopulations in murine MV/PVAT and human SAT. Cd28 + γδ NKTEM and Cd28 high δ TEM-cells increased in MV/PVAT from hypertensive mice and CD28 high δ TEM-cells in SAT from obese women compared to the lean women. Conclusion: Similar CD28+ δ T-cells were identified in murine MV/PVAT and human SAT. CD28high δ TEM-cells increased in MV/PVAT in hypertensive mice and in SAT from humans with obesity, a prehypertensive condition. CD28+ δ T-lymphocytes could have a pathogenic role in human hypertension associated with obesity, and could be a potential target for therapy.