The immunopathogenic mechanisms of a number of immune-mediated diseases and/or diseases characterized by abnormalities of immune function were investigated. We identified and characterized a phagocytosis-inducing factor (PIF) derived from the T cells of patients with granulomatous and erythrophagocytotic disorders, including the angioinvasive immunoproliferative diseases. These studies have important implications in understanding the mechanisms of secondary immune-mediated disease associated with specific T cell derived factors. We produced and characterized thyroid-derived T cell lines in autoimmune thyroid diseases (Graves' disease and Hashimoto's thyroiditis) and delineated the heterogeneity of abnormalities in B cell function in these diseases. In addition, we demonstrated the induction by interferon-q of HLA-DR antigens on thyroid follicular cells. These studies shed new insight into the role of viral infection-induced interferon production in the pathogenesis of autoimmune thyroid disease. We have extended our studies on the idiopathic hypereosinophilic syndrome (HES) and have demontrated that T cell clones from patients with eosinophilia and hyper-IgE secrete an antigen-specific factor which induces IgE isotype specific Ig secretion from B cells in vitro. Finally, we have demonstrated that patients with active systemic lupus erythematosus have circulating T cells which selectively secrete an IgG-specific B cell differentiation factor.
