FlipFlop mice have a reversed T cell immune system: MHC-I/CD8 Helper and MHC-II/CD4 Cytotoxic T cells

Almost all of T cells generate in the thymus. In the thymus, the fate of conventional T cells is determined as either CD4 T cells or CD8 T cells, which function mainly helper T cells or killer T cells, respectively, in periphery. To date, mechanisms underlying the fate determination of conventional T cells remain yet to be elucidated.
We recently generated unique “FlipFlop” mice in which both Cd4 and Cd8 gene loci encoded the opposite co-receptor protein. CD4 and CD8 T cells in FlipFlop mice recognize MHC-II and MHC-I ligands, respectively. Importantly, MHC-II/CD4 T cells in FlipFlop mice have cytotoxic function, while MHC-I/CD8 T cells have helper function. Thus, FlipFlop mice have a functionally reversed T cell immune system. As result, we propose that CD4/CD8 T cell lineage fate in the thymus might be determined by Cd4/Cd8 gene loci independently of the co-receptor proteins they encode and regardless of TCR MHC specificity.