Regulatory T cells selectively protect against experimental autoimmune encephalomyelitis induced with self but not foreign antigens (B79)

Abstract Naturally occurring CD4+CD25+ regulatory T cells (Treg) are selected in the thymus by self-antigens and can prevent the development of autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), can be induced with myelin oligodendrocyte glycoprotein (MOG). Here we show that both MOG mRNA and protein are detected in the thymus. To test whether Tregs specific for mouse MOG protect against EAE, we examined the effects of Treg depletion on EAE induced with the Ig-like domain of mouse (self), rat or human (foreign) MOGs. Treg depletion resulted in increased EAE severity following immunization with mouse MOG, but surprisingly, did not affect EAE induced with either rat or human MOG. The increase in disease severity following Treg depletion of mouse MOG immunized mice was associated with increased T cell proliferation and IL17 production as well as an increase in T cell response to the immunodominant peptide MOG35-55. In the central nervous system, T cells from mouse MOG immunized mice showed increased infiltration as well as increased ratio of IFNγ to IL10 producing cells following depletion. These data demonstrate the high specificity of Tregs to self but not foreign MOG, thus, underlining their inability to “cross-protect” against autoimmunity induced with closely related antigens. Supported by NMSS RG2394 and NIH CA16885.