In-Vitro Demonstration of Thymic Hormone in the Mouse by Conversion of Precursor Cells Into Lymphocytes

Induction of T-Cell Differentiation In Vitro by Thymin, a Purified Polypeptide Hormone of the Thymus

“…Using crude thymus extracts, Komuro and Boyse (8) also demonstrated this large population of mouse hematopoietic cells susceptible to differentiation by a thymus-inducing factor. Furthermore, they demonstrated that these susceptible cells were "pre-thymic," in that they could be identified in athymic nude mice (nu/nu) and in the hematopoietic cells of 14 day embryonic mouse liver obtained before the epithelial thymus had developed (9). The relationship of these cells to the "pre-T cells" identified by El-Arini and Osoba (23) remains to be clarified.…”

“…The antigens expressed represented products of several unlinked genes (8). The genetic background of the induced cells clearly dictated the nature of the products expressed, since cells from genetically TL negative mice could not be induced to express TL.…”

“…There have been many inherent difficulties in these studies, especially in the development of appropriate assays (1, 7). Recently, thymic differentiation has been detected more directly by demonstrating the expression of antigens characteristic of thymocytes on previously undifferentiated precursor cells (8,9).…”

Thymic control of proliferation of T cell precursors in bone marrow.

“…A hematopoietic hormone should have three activities: It should maintain its target cell and cause it to differentiate and proliferate (12). We have shown previously that the thymus extract maintains pre-T cells in vitro (3), and differentiation, at least to the extent of displaying new surface markers, is easily demonstrated (2,16). We show here that the third criterion is met in ivo, and thus that the thymus produces a hematopoietic hormone strictly analogous to colony-stimulating factors and erythropoietin.…”

“…First, the precursors of T cells (pre-T cells) develop in the bone marrow from pluripotential stem cells. These precursors can be demonstrated by their ability to reconstitute an irradiated recipient's thymus (1), by the induced expression of surface markers such as Thy-I and TL (2), and by their synergistic interaction with mature T cells in the response to mitogens (3). When pre-T cells reach some as-yet-undefined stage of development, they leave the bone marrow, and some find their way to the thymus, where the second, intrathymic stage of maturation takes place.…”