Previous reports have shown that CD4 help could be fully or partially independent of the CD40L/CD40 pathway [31], [55], [56], but our finding was somewhat surprising in light of a recent study showing that CD8+ T cells proliferating under lymphopenic conditions required CD4 help to induce autoimmunity and that this help was mediated by CD40 engagement on APCs [30]. The gene discussed is CD8A; the disease is Autoimmunity.