The disturbance in thiol expression characteristic of RA was investigated to determine whether it plays a role in the pathogenesis of the disease. This was studied by culturing mononuclear cells in a mitogen-driven system in vitro. Blockage of serum SH groups did not appear to influence mitogenic proliferation of mononuclear cells in vitro. However, mononuclear cell surface SH groups appear to be very much involved in both proliferation and immunoglobulin production. Both cell proliferation and antibody production can be abrogated by blocking the cell surface SH groups. It was shown that rheumatoid mononuclear cells produce less IgG than normal cells when stimulated with pokeweed mitogen in vitro. It was also shown that rheumatoid mononuclear cells will, however, make normal amounts of IgG following the addition, in vitro, of a simple thiol 2-mercaptoethanol (2-ME). Normal IgG synthesis was also observed by mononuclear cells from patients treated with D-penicillamine. The investigation showed that rheumatoid monocytes are defective accessory cells in the IgG production assay and that their function is corrected by 2-ME. However, both monocytes and lymphocytes must be incubated with 2-ME for normal IgG synthesis to occur. We have therefore demonstrated a membrane SH dependent interaction between monocytes and lymphocytes that is necessary for the production of IgG. The interaction does not appear to involve soluble mediators such as the interleukins or antigen presentation but rather the physical interaction between the lymphocytes and monocytes. This interaction is defective in RA and may be involved in the immunopathogenesis of the disease.
|Date of Award||1984|