In this review, we summarize the current understandings of T cell development, CD4+ and CD8+ αβ T cell and γδ T cell subsets, fate decision and regulation, functional roles in pathophysiological conditions, especially in infectious diseases, chronic infection and tumors and autoimmune diseases as well as immunotherapies harnessing T cell function in preclinical and clinical development. The gene discussed is CD4; the disease is autoimmune disease.