T Cell Cloning for the Investigation of the Mechanism Involved in Antirheumatic Effects of D-Penicillamine

Yamaki Fuyuhiko

For the precise evaluation of the mechanism involved in the antirheumatic effects of D-penicillamine (D-PC), we examined the inhibitory effects of D-PC on the clonal growth of human T cells. D-PC inhibited T cell clonal growth at 100μM or higher concentrations in the presence of cupper sulfate. However, such concentrations are much higher than that achieved by the usual dosage given in the treatment of rheumatoid arthritis (RA). Therefore, the mechanism, rather than the systemic effects, should be considered in the antirheumatic effects of D-PC. Since catalase completely reversed the inhibitory effects of D-PC on T cell growth, the generation of H_2O_2 was supposed to be the relevant mechanism. The growth of CD4 positive and CD8 positive T cells was similarly inhibited by D-PC. The frequency of T cells capable of forming colonies after treatment with 200μM. D-PC was measured in both healthy individuals and RA patients. Such T cells were assumed to be resistant to D-PC. The frequency of D-PC resistant T cells varied among both healthy individuals and RA patients who were not receiving D-PC. More than half of the RA patients who were receiving D-PC and showed good response had a frequency of D-PC resistant T cells around or lower than 10%. On the other hand, 80% of the RA patients with poor response to D-PC, or with an initial good response followed by disappearance of D-PC response, showed a D-PC resistant T cell frequency of higher than 20%. These results suggest that the frequency of D-PC resistant T cells in RA patients may be a clinical marker for the estimation of D-PC effectiveness prior to treatment.

T Cell Cloning for the Investigation of the Mechanism Involved in Antirheumatic Effects of D-Penicillamine

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