Inhibition of Capping of Surface Immunoglobulins at Femtomolsr Concentrations of Adriamycin, Compound ICRF-159 and Tetrodotoxin

arthritic patient. In both experiments the difference between the means is significant by Student’s t test ( P < 0.005), suggesting a decreased reactivity of lymphocytes from rheumatoid-arthritic patients t o phytohaemagglutinin compared with healthy controls. Preliminary experiments with control lymphocytes stimulated with protein A indicated that the optimum concentration of this mitogen was 10,ug/rnl. The results shown in Table 1 suggest that the optimum incubation period is 4 or 5 days. Table 2 shows the response of lymphocytes from controls and rheumatoid-arthritic patients to various concentrations of protein A when cultured for 4 days. The results of two trials are shown and a different control/patient pair was used ineachcase. As shown in Table 2, optimal stimulation occurs a t a protein A concentrationof IOpg/ml withcellsfromcontrolsandrheumatoid-arthritic patients. With concentrations of 80pglrnl or more the stimulation is only slight and probably not significant. However, over the range 5-5Opg of protein A/ml the stimulation of lymphocytes from rheumatoid-arthritic patients is decreased compared with control cells. At the optimum concentration (10pg/ml), the difference between the means is significant in both trials (P < 0.01). The decreased mitogenic response of lymphocytes from rheumatoid-arthritic patients t o phytohaernagglutinin suggests a possible defect in T-lymphocyte function, as has been previously suggested by other workers (Horwitz & Garrett, 1977). The response of cells from rheumatoid-arthritic patients to protein A suggests that B-lymphocyte function might also be impaired, despite the observed increase in immunoglobulin-rheumatoidfactor synthesis in such cases. Preliminary experiments following the incorporation of [3H]leucine in protein Astimulated lymphocyte cultures suggest that a similar response pattern will emerge for both D N A and protein synthesis.