In the last 30 months, we have found that T cells that respond to ApoB are protecting against early atherosclerosis. In fact, these cells exist in most healthy people. Most of these cells can be identified as T-regulatory cells, which are known to dampen immune responses. Thus, autoimmunity against ApoB is protective first. However, during atherosclerosis, this beneficial function is lost. We identified a loss of the important transcription factor FoxP3 as one of the important causes of this switch from protective to pathogenic phenotypes. The response of these atheroprotective cells may be boosted (at an early time-point) by vaccination with ApoB-peptide, but in the natural course of disease it is lost and replaced by a pathogenic phenotype. These findings indicate a potential paradigm shift in T cell biology in atherosclerosis and therefore represents an important breakthrough. That T cells are important for human atherosclerosis was shown by using a novel tool for quantified gene expression in single cells (single cell RNA-sequencing). Applying this tool to human atherosclerotic plaques, obtained after surgery, we showed that mouse atherosclerosis and human atherosclerosis are completely different from a cellular perspective: While mouse atherosclerosis is myeloid cell dominated (monocytes, macrophages), more than 60% of all leukocytes in human plaques are T cells. T cells from human tissue are also more activated than in the mouse. These data advance the field because they show that mouse models, which are most often used in atherosclerosis studies, are only of poor translatable value to investigate immunity, which has not directly been proven so far. We also showed that antibodies against ApoB-peptides correlate to clinical disease states in humans at high risk for atherosclerosis. These findings propose that adaptive immunity is one of the drivers of clinical disease in humans.