Title

Modulation of Autoimmunity by antigen specific regulatory T cells

Date of Completion

January 2010

Keywords

Health Sciences, Immunology

Degree

Ph.D.

Abstract

Multiple Sclerosis (MS) is a progressively debilitating human autoimmune disorder mediated by specific CD4+ effector T cells specific for myelin. The murine model for MS is Experimental Autoimmune Encephalomyelitis (EAE), which can be induced by immunizing with Central Nervous System (CNS) autoantigens like Myelin Oligodendrocyte Glycoprotein (MOG). Regulatory T cells have been shown to be very efficient in suppressing autoimmune responses like EAE. Therefore any method that can enhance the number of regulatory T cells or induce antigen-specific regulatory T cells can be extremely beneficial in controlling autoimmune diseases. This work shows, using a murine model of MS, that the Sympathetic Nervous System (SNS) and the Eye can both be used to modulate regulatory T cells in order to counter an autoimmune response: Peripheral ablation of the SNS results in an increase in the number of CD4+ Fox P3+ regulatory T cells, via a TGF-beta dependent mechanism. This enhanced number of CD4+ Fox P3+ regulatory T cells can suppress the induction of MOG induced EAE. An injection of MOG peptide into the ocular anterior chamber, results in the generation of MOG-specific CD4+ and CD8+ regulatory T cells that suppress EAE either at the priming or the chronic phase respectively. The work further shows that the mechanism of action of these eye-induced CD4+ and CD8+ regulatory cells is different and so is their migration pattern into the CNS. Overall, this work defines two unique ways to modulate autoimmunity. ^