CD4 and systemic sclerosis: Skin is predominantly infiltrated by CD4+ and CD8+ cytotoxic T cells that produce pro-fibrotic cytokines and cause apoptosis to epithelial cells [6,72]. Increased IL-21-producing Tph cells promote plasmablast differentiation and increase activation of myofibroblasts [75,77]. In the peripheral blood, SSc patients are characterized by increased Th2 and Th17 numbers compared to healthy donors [4,60,63].