Anti-human T lymphocyte porcine immunoglobulin attenuates experimental autoimmune encephalomyelitis by inhibiting T cell activation

Abstract

Abstract Anti-human T lymphocyte porcine immunoglobulin (P-ATG) is a type of anti-thymocyte globulin (ATG) drug that has been used as an immunosuppressant for severe aplastic anemia and graft-versus-host disease for decades. However, the potential application of ATG for the direct treatment of Multiple sclerosis (MS) and the immune regulatory mechanisms are still unclear. In this study, the therapeutic effects and possible underlying mechanisms of P-ATG were evaluated in the rat model of experimental autoimmune encephalomyelitis (EAE), the animal model of MS. P-ATG could bind to T cells in both human and rat PBMCs in vitro and inhibit inflammatory cytokines secretion from stimulated T cells. P-ATG treatment effectively ameliorated behavioral and pathological alterations in EAE rats through reducing inflammatory infiltration and demyelination in the spinal cords. Moreover, P-ATG treatment significantly suppressed the immune response of T cells, as indicated by a decrease in the IFN-γ + Th1 cell and IL-17 + Th17 cell proportions. These findings demonstrated that P-ATG attenuated EAE in rats by inhibiting the activation of helper T lymphocytes from naive T cells to Th1 and Th17 subsets. The therapeutic effect of P-ATG on EAE was independent of T lymphocyte depletion.