P177Apoptosis pathways are deregulated in CD4 + CD28null T cells from patients with acute coronary syndrome

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T lymphocytes, the main effectors of adaptive immunity, have key roles in the development and progression of atherosclerosis. One subset of T lymphocytes that is altered in patients with acute coronary syndrome (ACS) is the CD4 + CD28null T cells. These cells expand significantly in ACS patients compared to stable angina and healthy controls and have been suggested to mediate plaque instability and recurrence of acute coronary events. CD4 + CD28null T cells characteristically do not express the CD28 receptor which has pivotal roles for the activation and survival of T lymphocytes. Apoptosis is a homeostatic process that regulates the size of the T cell compartment. Very little is known about the mechanisms that lead to the accumulation of CD4 + CD28null T cells in ACS. Our aim was to characterise apoptosis pathways in CD4 + CD28null T cells in ACS patients to identify alterations that could explain the persistence of this cell subset.


We analysed the expression of death receptors (Fas) and ligands (FasL), as well as the levels of anti-apoptotic (Bcl-2, Bcl-xL, survivin) and pro-apoptotic (Bax, Bim) proteins in CD4 + CD28null T cells in patients with ACS using flow cytometry. In addition, we have quantified apoptosis sensitivity of in vitro activated CD4 + CD28null T cells using Annexin V and 7-AAD staining and detection of activated caspase-3.


We found that CD4 + CD28null T cells express significantly lower levels of the death receptor Fas compared to conventional CD4 + CD28 + T cells. Furthermore, the pro-apoptotic protein Bim was significantly decreased in CD4 + CD28null T cells compared to their CD28 + counterparts. Interestingly, CD4 + CD28null T cells failed to upregulate Bim following activation, in stark contrast to CD4 + CD28 + T cells. No differences were found in the levels of anti-apoptotic proteins between the two CD4 + T cell subsets.


We identified defects in the death receptor Fas and the pro-apoptotic protein Bim in CD4 + CD28null T cells from ACS patients which suggest that these cells are resistant to apoptosis. These findings could open the way for novel therapies aimed at targeted induction of apoptosis in CD4 + CD28null T cells to stabilise atherosclerotic lesions.

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