Research Focus

The overall goal of the research program in Dr. Woodward's lab is to understand the mechanisms of immunological tolerance toward self antigens.

It is clear that clones of T-lymphocytes with specificity toward self peptides exist in normal individuals, but that these clones are normally held in check by poorly understood mechanisms, operationally termed peripheral tolerance. Clonal deletion, clonal anergy, and active suppression have all been shown to participate in the generation of peripheral tolerance. A breakdown in peripheral tolerance results in autoimmune disease. One of the key goals of this research is to determine the behavior of the antigen specific T cell under conditions invoking immunity or tolerance and to understand the signals controlling each process. The Woodward lab is using a model system in which T cells from an ovalbumin-specific, T cell receptor (OVA-TCR) transgenic mouse are adoptively transferred into normal BALB/c mice. Since these OVA-TCR T cells can be visualized with the use of a monoclonal antibody, it is possible to determine the behavior of these T cells following immunization or tolerance induction. Following removal from the mouse, these T cells are analyzed by two and three color immunofluorescent staining and flow cytometry, immunohistochemistry, intracellular cytokine staining, and in vitro culture.

Ongoing projects in the lab concern the role of different tissues in peripheral tolerance induction using the eye as a model system, the role of the antigen presenting cell in tolerance induction, the ability of tumor cells to escape immune recognition by inducing a state of tolerance and, the production of transgenic mice as models of autoimmune disease to study the role of tolerance in regulating autoimmunity.

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