Figure 1.

Characteristics of CD4⁺CD28^null T cells in atherosclerosis. In patients that develop myocardial infarction due to coronary atherosclerosis CD4⁺CD28^null T cells have features that distinguish them from conventional helper CD4⁺CD28⁺ T lymphocytes. Specifically, CD4⁺CD28^null T cells express higher levels of alternative co-stimulatory receptors OX40 and 4-1BB, whereas co-inhibitory receptors (CTLA-4 and PD-1) are present in similar levels to those on CD28⁺ counterparts. OX40 and 4-1BB regulate the production of inflammatory cytokines [tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)] and the release of cytotoxic molecules (perforin, granzymes) by CD4⁺CD28^null T cells. Moreover, in these patients the expression of the death receptor Fas and of pro-apoptotic mitochondrial proteins Bim and Bax is significantly reduced in CD4⁺CD28^null T cells. This endows CD4⁺CD28^null T lymphocytes with resistance to apoptosis, which may allow these cells to accumulate and amplify inflammation and cause vessel wall damage, which may contribute to atherosclerotic plaque rupture.