The object of the research proposals are directed at studying immunologic intervention in autoimmunity. The clinical focus of this program project grant is the use of immunologic intervention in the treatment of rheumatoid arthritis by the use of total lymphoid irradiation by Dr. Strober. Closely aligned with this project is the proposal by Dr. Fathman to study collagen induced arthritis in rodents as a model of inflammatory autoimmune arthritis. A variety of immunnnotherapeutic protocols have been proposed with potential direct applications to human models. The studies outlined by Dr. Parnes are intended to investigate the basic immunoregulatory pathway which seems to be perturbed by the use of total lymphoid irradiation; that is, to down regulate the expression of major histocompatibility complex antigens on cell surfaces. The other projects have as their focus, systemic lupus erythematosis. The project by Dr. McDevitt uses an experimental new protocol in immunomodulation of a murine model of systemic lupus erythematosis, the NZB/WF1 glomerulonephritis. Preliminary data from Dr. McDevitt's laboratory suggest that the use of anti-Ia antibodies will have therapeutic significance in this disease. Thus, Dr. Engleman and Grumet propose to attempt to raise human antibodies reactive within MHC determinants which might be ultimately used for immunologic intervention in human autoimmune disorders, including systemic lupus erythematosis. The major thrust of this program project grant is an attempt to transfer technology which currently exists in the immunologic community at Standard to a more direct application toward potential patient care and immunologic intervention in autoimmunity. Each of these individual projects rely upon one or more of the compananion projects. It is through this type of integrated multi-department interaction that program project grants allow interactions among investigators that transcend the usual divisional or departmental boundaries of research activities and lead to more immediate technology transfer from the lab to patient care.
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