CD4 and acute graft versus host disease: Therefore, the autoreactive CD4+ T cells derived from the preexisting autoreactive CD4+ T cells in the graft play a major role in mediating chronic GVHD pathogenesis in recipients with overt acute and chronic GVHD, and the de novo-generated autoreactive CD4+ T cells from damaged thymus play a major role in chronic GVHD pathogenesis in recipients with little prior acute GVHD.