Induction of differentiation in human marrow T cell precursors by the synthetic serum thymic factor, FTS

The serum thymic factor, 'facteur thymique serique' (FTS), was analysed in vitro for its ability to induce differentiation of normal human marrow T cell precursors into cells with T lymphocyte characteristics. FTS has been isolated, characterized, sequenced and synthesized. In the mouse, natural and synthetic FTS have similar activities in vitro in the rosette inhibition assay. Both substances influence a variety of T cell differentiation markers and functions in vivo. In this study, we found that synthetic FTS induced appearance of two T cell surface markers, HTLA phenotypes and the ability to form E rosettes, on a selective population of normal human marrow cells sedimenting in layers II or III of a Ficoll discontinuous density gradient. In addition, a population of lymphoid cells also found in layer III, which bears receptors for peanut agglutinin (PNA), was decreased in number following exposure to FTS. In the same gradient layer, cells which expressed terminal deoxyribonucleotidyl transferase (TdT) activity showed decreased activity after treatment with FTS. Functional activities characteristic of T lymphocytes were also enhanced in marrow cells of gradient layer III after preincubation with FTS. These T cell functions were demonstrated in marrow cells by their ability to respond and to stimulate allogeneic peripheral blood lymphocytes (PBL) in mixed lymphocyte reactions and by responses to phytomitogens, PHA, Con A and pokeweed. These changes were not observed in marrow cells of gradient layers I, IV and V or after incubation with an FTS analogue that lacked biological and antigenic activity in the mouse system.