Specific receptors for the serum thymic factor (FTS) in lymphoblastoid cultured cell lines.

Abstract

The interaction of the synthetic serum thymic factor (FTS, "facteur thymique serique") with human T lymphocytes from two established T The thymus gland has been shown to produce a number of factors or "hormones" that promote the differentiation of thymus-derived cells (T cells) and induce the appearance of their specific markers. We showed in 1971 that thymic extracts induce the appearance of the best-characterized of these markers, the 0 (Thy-i) antigen, on 0-negative bone marrow rosette-forming cells (1). It was ultimately demonstrated that there exists in normal serum an active principle with activity on rosette-forming cells identical to that of thymic extracts. The absence of this principle in serum from thymectomized or nude (athymic) mice demonstrated the strict thymic dependence of this factor (2).The molecule responsible for this activity has been isolated from pig serum and called "facteur thymique senique" (FTS). FTS is a nonapeptide whose amino acid sequence has been determined. FTS has been synthesized, and the synthetic material shows full biological activity and displays chromatographical characteristics identical to those of biological FTS in several chromatography systems (3, 4).The recent observation of the localization of antibodies directed against synthetic FTS on the thymic epithelium has provided direct demonstration of its thymic origin.tThe binding to specific receptors on its target cell is the first step in the action of a polypeptide hormone. It is thus of utmost importance for the understanding of the cellular mode of action of FTS to search for and characterize FTS receptors on lymphoid cells. With this in view, we have applied the methodology now well established for polypeptide hormones (5). This effort was significantly helped by the finding of two lymphoblastoid cell lines that showed high levels of FTS binding. MATERIALS AND METHODSLymphoblastoid Cell Lines. The initial lymphoblastoid T cell line (1301) was given by S. M. Fu and M. Fellous. It was derived from a leukocyte culture of a patient with acute lymphoblastic leukemia. Lymphocytes were maintained at 370C in RPMI 1640 essential medium, supplemented with 10% fetal calf serum, 1% glutamine, antibiotics and, Fungizone. The cells were used in the binding studies when they were in the stationary phase of growth. Their viability was determined by their capacity to exclude trypan blue dye. The T cell nature of the cell line was established by the study of its markers (6, 7). Results of these studies are presented in Table 1. Methods used for marker evaluation have been previously reported (6, 7). Other cell lines were also studied in less detail. The origin, nature and characteristics of these various cell lines are presented in Table 1.FiTS. Labeled [3H]FTS was prepared according to a method consisting of lysine methylation by use of 3H-labeled sodium borohydride and formaldehyde (8). Briefly, 1 mg of synthetic FTS (Choay, Paris, France) was incubated for 1 hr at 40C with 100 mCi of NaB3H4 and 1 mmol of formaldehyde...

Immunological Evaluation of Patients with Beta-Thalassemia major

“…We demonstrate an abnormal distribution of lymphocyte subsets, such as a significant decrease of cell subpopulations expressing T cell markers and a significant enhancement of cells expressing B cell markers. It is known that thymulin binds to high-affinity receptors, induces several T cell markers, and promotes T cell function including allogenic cytotoxicity, suppressor function and IL2 production [55]. In our work we did not find a significant correlation between the active thymulin levels and the lymphocyte subset values expressing T cell markers, suggesting that additional mechanisms are involved in the explanation of immunological abnormalities in thalassemia.…”

Serum thymulin in human zinc deficiency.

“…These are thymopoietin and thymulin, both of which are produced by the thymic epithelium (1,2). Recent data demonstrate that thymulin binds to high-affinity receptors, induces several T cell markers, and promotes T cell function including allogenic cytotoxicity, suppressor function, and IL 2 production (20). For the first time, our study has provided evidence that even a mild deficiency of zinc may affect serum thymulin level.…”

Growth Hormone-Releasing Activity of Thymulin on Pituitary Somatotropes Is Age Dependent

“…In two tumor-derived human T-cell lines, two types of receptor for thymulin were found. One type was of high affinity (K d = 3.5 n M ) and the other was of low affinity (K d = 100 n M ), with no cooperative effects between receptors [31, 32]. No thymulin receptors have been reported, to our knowledge, in normal T and B cells.…”