IMMUNOREGULATORY MECHANISMS IN THE RHEUMATIC DISEASES

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The long-term objective of this proposal is to develop a greater understanding of the cellular components which mediate and regulate the human immune response. We plan to identify, characterize and look for abnormalities of newly described subsets of mononuclear cells found in the blood and tissues of patients with rheumatic diseases. We will continue to study "L" cells, a presumptive subset of non-T, non-B cells with high avidity Fc receptors for IgC. The precise relationship of L cells with other mononuclear cells will be investigated by characterizing cell surface antigens on L cells and other mononuclear cells with monoclonal antibodies produced by hybridomas. Flow cytofluorography will be utilized to accomplish this task. Secondly, specific cell-types will be separated on the basis of cell surface markers by cell-sorting and the functional properties of purified cells will be compared using in vitro techniques. We will investigate L cells-T cells interactions in the regulation of B cell function. Thirdly, L cells are excellent mediators of spontaneous or natural killer antibody-dependent cellular cytotoxicity. A comparison of the cytotoxic effects of L cells with other cell types will be continued. Finally, we plan to learn the significance of a cellular cytotoxicity defect we have recently described in rheumatoid arthritis. Studies will be conducted to define the effector cells and regulatory cells involved in this defect, to learn whether this defect may be an important pathogenetic factor in rheumatoid arthritis and to investigate possible means of correcting this defect. It is likely that a better understanding of regulatory abnormalities in patients with rheumatic diseases will lead to new and safer approaches to control these disorders.