Despite CD4+ T-cells are more resistant to age-related phenotypic and functional changes than CD8+ T-cells (Weinberger et al., 2007), a progressive increase in the percentage of CD4+ T-cells that lack CD28 expression is common with increasing age in healthy individuals (Goronzy et al., 2007; Czesnikiewicz-Guzik et al., 2008) and in patients with chronic infections and autoimmune diseases (Fletcher et al., 2005; Thewissen et al., 2007). Here, CD4 is linked to autoimmune disease.