In SSc CD8+CD28− cells both in peripheral blood and in skin were found to express the effector/EM phenotype and expressed high levels of perforin and granzyme B [86] while in PM and DM CD8+CD28− cells produced more pro-inflammatory TNFα than CD28+ cells on stimulation with anti-CD3 and 98% of CD8+CD28− cells expressed perforin [88]. This evidence concerns the gene CD28 and systemic sclerosis.