CHARACTERIZATION OF THE IMMUNOREGULATORY CIRCUITS IN MAN

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Recent studies demonstrate that human T cell pool is heterogeneous with respect to cell surface markers and functional programs. Moreover, the cells which comprise the regulatory circuits controlling help and suppression are still poorly defined despite their importance in a host of human diseases, including autoimmune and immunodeficiency disorders. We believe, given the major recent technical breakthroughs in the definition of cell surface markers, functional assay systems, and cloning techniques, that one can develop important new insights into the immunoregulatory circuit in man. Furthermore, we have just developed a new set of monoclonal antibodies which define the T4 suppressor inducer subset (anti-2H4 antibody) and the T4 helper inducer subset (anti-4B4 antibody) that will help in the resolution of the heterogeneity of T4 cells. To characterize the immunoregulatory circuit in man, we plan to take advantage of the recently developed primary in vitro anti-DNP antibody forming system. This system allows for a precise examination of cell-cell interactions involved in the generation of supression of anti-DNP antibody production and for the characterization of the factors released by immunoregulatory T cells. Furthermore, we plan to develop KLH specific T cell clones which have unique regulatory activities. In addiiton, we plan to analyze the T cell subsets, functions of isolated cells, and fine specificity of naturally occurring anti-T cell antibodies in patients with systemic lupus erythematosus, juvenile rheumatoid arthritis, and Sjogren's disease. We believe that the analysis of both normal cells and cells from patients with autoimmune disease will provide new insights into the heterogeneity of the diseases and the complexity of the immunoregulatory circuit. It is hoped that a better understanding of the regulatory circuits in man will be critical for both an understanding of the basic biology of the human lymphocytes and for an understanding of disorders of lymphocytes which are present in a host of human diseases. Lastly, it is believed that rational therapy depends on the precise understanding of the immunoregulatory circuit.