Inhibitory factor(s) of lymphoproliferation produced by synovial fluid mononuclear cells from rheumatoid arthritis patients: the role of monocytes in suppression.

Synovial fluid (SF) and synovial fluid mononuclear cells (SFM) were obtained from patients with rheumatoid arthritis (R.A.). The SF stimulated normal blood monocytes for nitroblue tetrazolium (NBT) reduction and inhibited normal lymphocyte response to PHA. Similar activities were found in supernatants from the cultures of SFM cells. Molecular weight of the lymphocytes inhibitory factor(s) produced by SFM was in range 50,000 to 100,000. The factor exerted its inhibitory activity via monocytes and had no direct toxic or blocking effect on lymphocytes. Monocytes played an active role in suppression presumably via production of a second-step inhibitory signal(s). It is suggested that the monocytes activated by the SFM-produced factor(s) are in turn triggered on for suppression of lymphoproliferation. These studies implicate that the state of monocyte activation is important in the regulation of lymphocyte responsiveness. This model of suppression may provide some explanation for SF lymphocyte hyporeactivity to mitogens in R.A.