Zsuzsanna Fabry, PhD
Department of Pathology and Laboratory Medicine
Immunopathology; neuroimmunology; multiple sclerosis
There are a number of important human central nervous system (CNS) diseases of poorly understood autoimmune etiology which are characterized by the presence of inflammatory cell infiltrates in the CNS and immune-mediated disruption of CNS function. One example is Multiple Sclerosis (MS) which is a chronic inflammatory diseases of the CNS. The pathogenesis of this isease is very difficult to understand for the following reasons:
- The autoantigen against which the initial immunopathological response is directed is largely unknown.
- The cell types presenting the autoantigens are not well identified.
- No single immune mediator or cell have been pinpointed as a key factor in damaging the local tissue elements.
- The mechanism of T cell migration across the blood-brain-barrier and the immunological survey of the CNS are not well understood.
For several years, I have focused my attention on studying the interactions between the cellular elements of brain microvessels and T lymphocytes and the role of such interactions in promoting inflammatory diseases of the central nervous system. Our studies on T cell migration into the CNS have led us to characterize the important role of transforming growth factor beta (TGF-b) in regulating inflammatory reactions in the nervous tissue. Our laboratory had also characterized several cellular and molecular signals involved in the regulation of T-lymphocyte adhesion, migration and activation at the brain microvessel wall. The goal of our studies is to understand the role of T cells in CNS autoimmune inflammatory reactions and to design new treatment for CNS inflammatory diseases. Conventional techniques and experimental procedures are incapable of addressing this issue definitively, therefore, we are currently using novel transgenic strategies, enabling us to follow a monoclonal T cell population and inducible antigen expression in the CNS. We believe that the successful completion of this research project will lead to an improved understanding of the specific role of T cells in CNS inflammatory diseases and will provide the foundation for new therapeutic ways aimed at controlling of CNS inflammation.