27th European Cardiology Conference

Biography

Biography: Ingrid E. Dumitriu

Abstract

We have previously shown that CD4⁺CD28^null (CD28^null) T cells are a unique T lymphocyte subset with pro-inflammatory and cytolytic function. CD28^null T cells increase in the circulation and atherosclerotic plaques of myocardial infarction (MI) patients. CD28^null T cells accumulate preferentially in unstable atherosclerotic plaques and promote atherosclerotic plaque rupture via release of their cytotoxic cargo and lysis of endothelial and vascular smooth muscle cells. MI patients with high CD28^null T cell numbers have increased risk of recurrent severe coronary events and unfavourable prognosis. The precise mechanisms that regulate the inflammatory and cytolytic functions of CD28^null T cells in MI remain elusive. We performed whole genome transcriptome analysis of CD28^null and conventional CD28⁺ T cells from MI patients to identify differences in gene signatures between these two lymphocyte subsets. We found that CD28^null T cells from MI patients had marked differences in gene programmes compared to conventional CD28⁺ T cells. Functional enrichment pathway analysis revealed the natural killer cell mediated cytotoxicity and chemokine signalling pathways as the most significantly up-regulated. We provide data confirming these changes at protein level and demonstrating their impact on the function of CD28^null T lymphocytes. Our novel findings reveal that the distinct phenotypic and functional properties of CD28^null T cells are regulated at transcriptional level and identify novel molecular targets to modulate the deleterious function of this cell subset in MI patients.