In ApoE-deficient mice, a high-fat diet shifted T cells toward an exhausted state, strongest in the aorta. After 24 weeks, exhausted cells made up 15.7% of pooled T cells on a high-fat diet versus 10.6% on a vegetarian diet. Switching to the vegetarian diet after 12 weeks of high-fat feeding restored that proportion to 10.6%, though some tissue-specific gene-expression changes lingered. Clonal expansion in the aorta tracked with exhaustion score (Spearman 0.57), and aortic macrophages showed inflammatory, antigen-presenting profiles consistent with chronic T-cell stimulation.
The evidence comes from mice, not people, so it cannot yet guide personal choices. Still, the finding is intriguing: it suggests diet-driven vascular inflammation involves T-cell dysfunction as well as cholesterol and macrophages, and that the damage is only partly reversible. The "durable imprint" framing echoes human data showing early lifestyle change yields benefits that outlast the intervention, and hints at why cumulative dietary exposure matters. Caveats are substantial: ApoE-knockout mice are an extreme model of atherosclerosis, the "vegetarian diet" comparator is a chow formulation rather than a matched low-fat diet, so fat quantity and composition are confounded, and the clonotype correlation rests on a small number of clones (p = 0.029). Macrophage-T cell communication was computationally predicted rather than directly tested, and no cardiovascular outcomes were measured. This is a preprint that has not been peer reviewed, so results may change. Editorially, it is incremental and hypothesis-generating, adding immune detail to a well-established link between dietary fat and atherosclerosis.