Human postthymic precursor cells in health and disease. IV. Abnormalities in immunoregulatory T cell circuits in mixed connective tissue disease.

Human T cells are capable of forming rosettes with autologous erythrocytes (Tar cells) and behave as postthymic precursors. Thus, they generate Tgamma and Tmu cells as well as suppression and spontaneous cytotoxicity and participate in a pokeweed mitogen-driven system akin to that of feedback inhibition in which murine postthymic precursors participate. Tar cells were increased in 7 patients with mixed connective tissue disease (MCTD) compared to normal age/sex-matched controls. Despite this increase of precursor cells, decreased Tgamma cells and abrogation in the generation of suppression and of feedback inhibition were noted. These functional defects were not correctable with serum thymic factor but could be corrected by the addition of either allogenic Tmu or mononuclear cells depleted of Tar cells. Our findings suggest that the immunoregulatory T cell circuits in MCTD may be adequate both in postthymic precursor cells and in the thymic factor prompting. They are probably abnormal either at the site of Tmu signaling to Tar cells in feedback inhibition or in the Tmu reception of suppressor signals from Tgamma cells. The decrease of Tgamma cells in MCTD could be due to the decreased stimulus from feedback inhibition and/or to the penetration of anti-ribonucleoprotein antibody. Abnormalities of immunoregulatory T cell circuits in MCTD are quite different from those found previously in systemic lupus erythematosus, scleroderma, and rheumatoid arthritis. These differences support the notion that MCTD is a distinct entity.