Myelin basic protein specific TCR-engineered regulatory T cells from multiple sclerosis patients are suppressive to MBP-specific T effector cells

Abstract Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by inflammation, demyelination and axonal injury. Expanded T regulatory cells have been used in clinical trials for autoimmune diseases, but CNS-specific cells are rare in polyclonal populations and have the potential to be non-specifically immunosuppressive. Previously, we developed MS-specific Tregs by transducing a MBP-specific T-cell receptor (Ob2F3 TCR) into expanded human Tregs. Ob2F3 TCR-transduced Tregs successfully suppressed MBP-specific Ob2F3 T effector cells in vitro as well as MOG-induced EAE in vivo (Kim et al., J. Autoimm. 92: 77–86, 2018). However, Tregs in MS patients have been reported to be impaired in their suppressive function. Herein, we transduced Tregs from MS patients and healthy controls and tested them for suppression of effector T-cells to determine whether this activity is significantly different with patient Tregs. Treg (CD4+CD25hiCD127low) and naïve T-cells (CD4+CD25lowCD127hi) were isolated from peripheral mononuclear cells and retrovirally transduced with specific the Ob2F3 MBP-specific TCR, expanded and tested for suppression in vitro. We found that MBP-specific Tregs isolated from MS patients maintain Treg markers and are able to inhibit autologous MBP-specific T effector cells as well as MBP-specific Tregs from healthy controls. Our data suggest that Tregs obtained from MS patients can retain their suppressive function upon expansion and transduction with the MBP-specific TCR, and could be used therapeutically to restore a tolerance in patients. (Supported by NMSS RG1612-26484 and NIH Intramural funds)