Role of cytomegalovirus in driving cytotoxic CD28null T cells

Accumulation of CD28null T cells has been traditionally considered a sign of aging, as the percentage of these cells is increased in the elderly. However, the permanent loss of CD28 on T cells is caused by chronic antigenic stimulation. In that sense, CMV infection seems to be an important factor, particularly in the CD4 T-cell compartment, where significant expansions of these cells have been observed in CMV-seropositive individuals only and independently of age. In contrast to this, the CD28null CD8 T-cell subset is more heterogeneous, consisting of different type of cells with diverse origins, phenotype, and functions. Indeed, contrarily to their CD4 counterparts, CD28null CD8 T cells can be found expanded in the absence of CMV. CD28null CD4 T cells are cytotoxic and produce high amounts of pro-inflammatory cytokines. Expansions of these cells has been shown to be associated with many diseases and seems to have a relevant role in CVD (cardiovascular diseases). We, therefore, propose that CMV-related CVD risk may be mediated in part by CD28null CD4 T-cells, capable of damaging the vasculature.