Interrelationships of immunoregulatory cells and serum factors in sarcoidosis

We studied cellular and plasma-related immunomodulatory factors in 12 patients with stage II sarcoidosis. Six patients showed depressed ³H-thymidine incorporation induced in peripheral blood mononuclear cells (PBMC) by phytohemagglutinin (PHA), streptokinase-streptodornase (SKSD), tetanus toxoid, and candida antigens; six patients had normal responses. Adherent cell depletion increased T lymphocyte responses to PHA 3-fold and to SKSD 6-fold in low responders but did not significantly affect the responses of the other sarcoid patients. Add-back experiments confirmed the presence of a suppressor adherent cell population in low responders. Indomethacin treatment of PBMC only partially restored PHA responsiveness; thus, production of immunosuppressive prostaglandins does not account for suppressor cell activity in sarcoidosis. Monocyte attachment to plastic was studied as an index of alterations in the cell surface reflecting activation. Sarcoid PBMC in sarcoid plasma showed a 50% increase in attachment compared with normal PBMC. Sarcoid plasma also significantly increased the adherence of normal PBMC to plastic, although not to the level of sarcoid cells in sarcoid plasma. The adherence-augmenting principle in sarcoid plasma was reversible in its action, heat-labile, and non-dialyzable. Furthermore, it eluted in the 20,000 to 30,000-dalton range on Sephadex G-100 chromatography and inhibited the migration of PBMC from agarose droplets. Pooled sarcoid plasma also suppressed responses of both normal PBMC and T lymphocytes to antigens and mitogens, suggesting that the inhibitory effect of sarcoid plasma was not mediated solely through an effect on monocytes. In 8 sarcoid patients, 37°C heat-stable T lymphocyte E-rosettes were increased to a mean of 18.8% compared with a mean in normal controls of 4.2%. Depletion of 37°C stable rosettes from PBMC decreased PHA responsiveness, suggesting that these cells were a responsive rather than a suppressor population. These studies demonstrate suppressor adherent cells in some patients with sarcoidosis and serum factors that suppress lymphocyte function and may contribute to monocyte activation.