The objective of the proposed program project is to continue a 23-year program of research directed toward and examination of the role of immunologic processes in the pathogenesis of various rheumatic diseases. The proposed program consists of six separate projects that are tied together by their emphasis on the immunopathogenesis of various rheumatic diseases. The first two projects will examine immunoregulatory abnormalities in systemic lupus erythematosus and rheumatoid arthritis, respectively. A detailed analysis of abnormalities in T and B cell function in SLE will be carried out in project I (Immunoregulatory Abnormalities in Systemic Lupus Erythematosus, Peter E. Lipsky, M.D., Principal Investigator) whereas project 2 (Immune Regulation of Rheumatoid Factor synthesis, Hugo E. Jasin, M.D., Principal Investigator) will focus on immunoregulatory abnormalities that predispose to rheumatoid factor production in patients with rheumatoid arthritis. The second two projects will focus on the regulation of lymphocyte traffic by the microvasculature. Project 3 (Immunobiology of the Dermal Microvascular Unit, Richard Sontheimer, Principal Investigator) will focus on a detailed analysis of the interplay of 3 major cells of the dermal microvascular unit, the dermal microvascular endothelial cell, perivascular monocyte, and T cell and abnormalities in the function of this group of functionally important cells in diseases such as systemic lupus erythematosus. Project 4 (Lymphocyte-EC Interactions in Chronic Inflammation, Nancy Oppenheimer-Marks, Ph.D. and Druie Cavender, Ph.D., Co- Principal Investigators) will focus on a detailed analysis of the physiology of the interactions between endothelial cells and circulating T cells and the control of these interactions at inflammatory sites. Finally, two projects will focus on the immunopathogensis of ankylosing spondylitis and reactive arthritis. The first of these (Analysis of the Bacterial Etiology of Reactive Arthritis, Heather Stieglitz, Ph.D., Principal Investigator) will attempt to discover the bacterially encoded antigen that triggers reactive arthritis, whereas the second project (Experimental Arthritis in Transgenic Rates & Mice, Joel D. Taurog, M.D., Principal Investigator) will utilize HLA B-27-expressing transgenic mice and rats to determine the role of this class I human histocompatibility gene product in the etiology of the spondyloarthropathies. The program project as a whole thus will address a number of problems pertinent to the immunopathogenesis of rheumatic diseases. Although a number of different specific questions will be analyzed, the central thrust of the program remains the detailed analysis of immunologic factors in the induction and expression of rheumatic diseases.
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