Activated lymphocytes in the peripheral blood of patients with rheumatoid arthritis

The peripheral blood and synovial fluid of patients with rheumatoid arthritis (RA), when compared to controls, has a higher proportion of mononuclear cells actively synthesizing DNA (S-phase cells). Such cells can be marked by radioautography after incubation with tritiated thymidine and can also be quantitated by the 4-h spontaneous in vitro uptake of tritiated thymidine. As our previous studies showed a marked and rapid decrease in this latter measure, in response to in vivo methotrexate, we suggested that the responsible cells may have a direct role in pathogenesis rather than merely reflecting the inflammation that is present. We have therefore tried to characterize them further. A mean of 46% of these autoradiography positive cells from the peripheral blood of patients with active RA bear CD3 markers and 61% Ia. On some occasions up to 25% stain for Leu M3 and 25% for Leu 7. None were esterase positive. Cell separation studies confirm that such cells were found in both T cell and non-T cell enriched populations. These cells, therefore, appear to be heterogeneous. A decreased number was seen in peripheral blood lymphocytes from patients who had received remittive therapy for over 4 months when compared to other patients with RA and this was associated with a lower 4-h spontaneous uptake of labelled thymidine.