In T1D where the destruction of pancreatic β cells is primarily mediated by CD8+ T cells, IL-21-producing Tfh cells are increased significantly784 and IL-21R expression is elevated in CD8+ T cells.795 While IL-21 overexpression drives T1D development,795 IL-21R deficiency inhibits T1D mellitus.796 The functions of autoreactive CD8+ T cell responses in autoimmunity will be discussed in later chapter. This evidence concerns the gene IL21 and type 1 diabetes mellitus.