A cellular deficiency in the rheumatoid one-way mixed lymphocyte reaction

Activated lymphocytes expressing transferrin receptors (TFR) are present in the peripheral blood in rheumatoid arthritis. Characterization of these cells shows a CD4 dominance with depressed expression of CD8 and NK antigens, similar to synovial infiltrates. In the present study, one-way mixed lymphocyte reactions were performed to compare the response of rheumatoid patients with that of normal individuals. The TFR+ cells generated were characterized by double-label immunofluorescence. The TFR+ cells from rheumatoid responders showed elevated CD4+ cells and depressed CD8 and Leu-7 (NK) expression compared with normal, throughout the response. This defect was corrected by adding recombinant interleukin 2 at the beginning of the culture period. CD8+ cells stimulated to express TFR following interleukin 2 supplementation of the rheumatoid responses co-expressed HLA-DR. Functional studies indicated that TFR+ CD8+ cells were not cytotoxic, indirectly suggesting them to be suppressor cells. These findings indicate that significant immunoregulatory abnormalities in rheumatoid arthritis may reflect abnormal interleukin 2 biology.