Double negative T cells (CD3+CD4-CD8-, DN T cells), a small subpopulation of CD3+ T lymphocytes, appear in secondary lymphoid organs and peripheral blood of healthy individuals including human and mice, which contributes to physiological immunological responses against intracellular pathogens, influence long-term allograft survival and prevent autoimmune disease [59–61]. This evidence concerns the gene CD4 and autoimmune disease.