CD8A and lymphopenia: A wealth of evidence indicates that DN T cells derive from CD8αβ+ T cells: (a) CD8+ and DN T cells share Vβ usage and CDR3 sequences (19); (b) mice deficient in β2-microglobulin or MHC-I molecules have reduced numbers of DN T cells (20–22); (c) the Cd8a locus is hypomethylated in DN T cells, indicating previous transcriptional activity (23, 24); (d) CD8+ T cells lose CD8 when they encounter cognate antigen presented as self (25, 26); (e) DN T cells can upregulate CD8 when they undergo homeostatic proliferation under lymphopenia (27).