Human Postthymic Precursor Cells in Health And Disease

Abstract

Human T cells are capable of forming rosettes with autologous erythrocytes (Tur cells) and behave as postthymic precursors. Thus, they generate T, and T, 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. T,,, cells were increased in 7 patients with mixed connective tissue disease (MCTD) compared to normal agelsex-matched controls. Despite this increase of precursor cells, decreased T, 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 T, or mononuclear cells depleted of T,, 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 T, signaling to T,, cells in feedback inhibition or in the T, reception of suppressor signals from T, cells. The decrease of T, cells in MCTD could be due to the decreased stimulus from feedback inhibition andor 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. Controversy exists about whether mixed connective tissue disease (MCTD) is a distinct entity or a subset of systemic lupus erythematosus (SLE) (1-3).In both diseases, patients have decreased circulating T, cells (1,4) and loss of suppressor cell function (1,5,6). Patients with SLE, however, may show a heterogeneity between the results of spontaneously expanded and concanavalin A (Con A) induced suppressor cell functions (7), whereas both of these functions are decreased homogeneously in MCTD (1).Spontaneously expanded and Con A-induced suppressor functions are generated by postthymic precursor cells which are distinguishable as well as separable in humans by their property of forming rosettes with autologous erythrocytes (8). Circulating mononuclear cells (MNC) from patients with SLE have decreased proportions of autologous rosetteforming T cells (Tu, cells) and T,, cells from SLE patients have a decreased capacity of generating suppression (9). Cells from SLE patients also function poorly in a pokeweed mitogen (PWM) driven system where T,, cells provide suppression under the influence of T, cells and help under the influence of T, cells. This functional property resembles murine feedback inhibition which can be defined as the induction of T suppression on B cells by helper T cells signaling unprimed postthymic precursor T cells (9); thus we have designated this phenomenon human feedback inhibition. These abnormalities of the T,, cells from the peripheral blood of SLE patients are partially correctable with serum th...