T CELL VLA-4 OVEREXPRESSION IN LUPUS AND VASCULITIS

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The applicant proposes funding with the intent of improving the current understanding of the role of VLA-4 in the pathogenesis of vasculitis in autoimmune diseases. The proposal ius also a natural extension of the applicant's current research. The applicant has recently shown that murine T cells transfected with CD18 will overexpress another adhesion molecule., LFA-1, and become autoreactive. Adoptive transfer of these autoreactive T cells causes a lupus-like autoimmune disease in syngeneic mice. Recent study has shown that a subset of T cells from lupus patients also overexpress LFA-1 and are autoreactive. Interestingly, only lupus patients with vasculitis have T cells that overexpress both LFA-1 and VLA-4. The role of VLA-4, and other T cell surface molecules with adhesion function such as CD2, in the pathogenesis of vasculitis and autoimmunity is currently unknown. The applicant proposes to cause murine T cells to overexpress VLA-4 and CD2, with and without concurrent LFA-1 overexpression, by transfection experiments. The in vitro significance of VLA-4 and CD2 overexpression of T cell autoreactivity and T cell adhesion functions will be explored. The in vivo significance of the in vitro changes will then be determined by adoptive transfer experiments. The principal investigator is applying for support as an independent new investigator. The applicant has recently assumed a tenure track position as an Assistant Professor in the Division of Geriatrics and Rheumatology at the university of Michigan in December, 1996.