Genetically Modified Hematopoietic Stem/progenitor Cells That Produce IL-10–secreting Regulatory T Cells

SignificanceAmino acid copolymers that are used in the treatment of experimental autoimmune encephalomyelitis (EAE) in mice or multiple sclerosis (MS) in humans result in the induction of immunosuppressive IL-10–secreting regulatory T cells. The TCRs of these T cells have previously been isolated and sequenced. Introduction of these TCR into a retroviral vector was used to transduce murine hematopoietic stem/progenitor cells (HSC/HPC). These genetically modified HSC/HPC were then transplanted to create retrogenic mice. Splenocytes or T cells of these retrogenic mice produced high levels of IL-10 on appropriate stimulation, and strongly suggests that the TCR itself encodes information for IL-10 secretion. Moreover, these retrogenic mice were resistant to induction of EAE, suggesting an approach to therapy for progressive MS using genetically modified HSC/HPC for transplantation.