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Mechanisms
of Autoimmunity
Dr. Wofsy’s research is focused on the cellular and molecular mechanisms
that lead to autoimmune diseases. For many years, this work was conducted
in murine models for systemic lupus erythematosus (SLE), but in recent
years Dr. Wofsy has become increasingly involved in clinical trials of
new therapies in humans. The principal strategy of the work in murine
models has been to use monoclonal antilymphocyte antibodies (mAb) or
recombinant fusion proteins to inhibit selected lymphocyte subsets, surface
molecules, or secreted products in mice that spontaneously develop an
illness that closely resembles SLE in people. This research has two closely
related goals. First, by inhibiting selected targets in lupus-prone mice,
Dr. Wofsy seeks to determine the role of distinct cell subsets, surface
molecules, or cytokines in the pathogenesis of autoimmune disease. Second,
by identifying components of the immune system that promote SLE, Dr.
Wofsy seeks to develop new approaches to the treatment of autoimmune
diseases.
Dr. Wofsy’s research first demonstrated the critical importance
of CD4+ T cells in promoting murine lupus, and then suggested the use
of non-depleting anti-CD4 mAb in the treatment of autoimmune diseases
in humans. Subsequently, Dr. Wofsy and his colleagues showed that selective
inhibition of T cell costimulation via CD28 and/or CD40-ligand could
produce profound benefit in lupus-prone mice. Based in part on these
observations, Dr. Wofsy is now conducting clinical trials designed to
determine whether inhibition of T cell costimulation can be effective
in people with SLE.
Selected Publications:
Kalunian KC, Davis JC, Merrill JT, Totoritis, Wofsy D: Treatment of systemic
lupus erythematosus by inhibition of T cell costimulation with anti-CD154:
A randomized, double-blind, placebo-controlled trial. Arthritis Rheum
46:3251-3258, 2002.
Daikh DI, Wofsy D: Cutting edge: reversal of murine lupus nephritis with
CTLA4Ig and cyclophosphamide. J Immunol 166:2913-2916, 2001
Daikh DI, Finck BK, Linsley, PS, Hollenbaugh D, Wofsy, D: Long-term inhibition
of murine lupus by brief simultaneous blockade of the B7/CD28 and CD40/gp39
costimulation pathways. J Immunol 159:3104-3108, 1997.
Contact Information:
Email: dwofsy@itsa.ucsf.edu
Phone: 415/750-2104
Address: Box 111 R, VAMC Bldg 2 53
The University of California, San Francisco, CA 94143, (415) 476-9000
Copyright 2003, The Regents of the University of California.
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