Ingrid E. Dumitriu
St. George’s University of London, UK
Title: Deregulations in CD4+ T lymphocytes subsets promote inflammation in atrial fibrillation
Biography
Biography: Ingrid E. Dumitriu
Abstract
The precise role of inflammation in the development and perpetuation of atrial fibrillation (AF) is yet to be fully uncovered. T and B lymphocytes, the main cellular effectors of adaptive immunity, have pivotal roles in orchestrating inflammation. Different subsets of lymphocytes either promote or prevent inflammation. We are investigating a unique subset of lymphocytes, the CD4+CD28null T cells that expand in patients with chronic inflammation. These cells secrete high levels of pro-inflammatory cytokines tumour necrosis factor-α (TNF-α) and interferon-g (IFN-g). The response of CD4+CD28null T cells is normally maintained under control by regulatory T cells (Treg), a specialised subset of T lymphocytes with suppressive function that maintain immune homeostasis and prevent pathogenic immune responses. The role of CD4+CD28null and Treg cells has not been investigated in AF. We found that CD4+CD28null T lymphocytes were significantly increased in the circulation of AF patients compared to controls (p<0.0001). In addition, AF patients had a marked reduction (p=0.0001) in Treg cells. The ratio of CD4+CD28null T lymphocytes to Tregs was significantly increased. In contrast, no alterations were identified in circulating B cell subsets. Levels of hsCRP, TNF-α and IFN-g did not correlate with CD4+CD28null T cell and Treg frequency. Instead, we demonstrate that the expansion of CD4+CD28null T cells is caused by defects in apoptosis pathways and increased activation and proliferation in response to homeostatic cytokines. These novel results suggest an imbalance in the mechanisms that maintain homeostasis in the immune response, which may promote inflammation in patients with AF.