Stimulation of lymphocytes from rheumatoid arthritis patients by mitogens and IgG.

In the first part of this work patients with rheumatoid arthritis (RA), 36 cases and normal subjects, 49 cases have been studied by lymphocyte cultures stimulated by phytohaemagglutinin (PHA), Concanavalin A (Con A), pokeweed mitogen (PWM) and Con A convalently bound to sepharose 4 B (Con A-S). The comparisons between the two groups have shown a significant difference between the RA lymphocytes and the control lymphocytes stimulated by PHA and Con A. However no statistical difference has been found between the two lymphocytes populations stimulated by PWM and Con A-S. In view to determining the lymphocyte population stimulated by each mitogen, separations of B- and T-cells from peripheral blood have been performed according to the ability for the T-cells population to bind the sheep red blood-cells (rosette forming cells). The T-cell rich population was only stimulated by PHA, Con A and PWM. Although the T-cell depleted one has shown no response to these mitogens, a response to Con A-S was elicited. In the second part of this work, patients with RA, patients with positive tuberculin (PPD) skin-tests and controls were studied. The lymphocytes from these groups were cultured in serum-free medium to obtain cell-free supernatants. These lymphocyte cultures were preincubated with the appropriate antigen or reconstituted after removal of the cells. Supernants from RA lymphocytes stimulated in vitro by undenaturated IgG induced an inhibition of the leucocyte migration, as well as the supernatants from tuberculin-sensitized lymphocytes. However, supernatants from non-RA lymphocytes or tuberculin-unsensitized lymphocytes did not show such an inhibition. These MIF like supernatants have been studied by Sephadex G-100 gel filtration. A MIF like activity has been found for PPD and IgG supernatants between the chymotrypsinogen (MW 23,000) and the lysozyme (MW 17,000). This MIF like activity could be due to RA lymphocytes stimulated by undenatured IgG.