High-fat diet promotes exhaustion-associated T-cell remodeling across vascular and lymphoid tissues in atherosclerosis-prone mice

A 12-week study on mice fed either a vegetarian diet or a high-fat diet revealed that the latter led to increased exhaustion-associated T-cell states in various tissues. At 24 weeks, these exhaustion-associated cells made up 15.7% of the total T-cell population in mice on high-fat diet, compared to 10.6% in mice on a vegetarian diet.

Restoring the diet to a vegetarian one for 12 weeks brought the exhaustion-associated cell proportion back to 10.6%. However, some transcriptional changes remained in different tissues after this dietary reversal. Aortic macrophages in the high-fat diet mice showed signs of inflammation and antigen presentation, along with increased communication with T cells.

The aortic T-cells showed increased activation and clonal expansion, with the size of these clonotypes correlating with the exhaustion score (Spearman correlation coefficient = 0.57, p = 0.029). These findings suggest that a high-fat diet can leave a long-lasting impact on the adaptive immune system in multiple organs during the development of atherosclerosis.