Thymic Hormones and the Immune System

Abstract

The central role of the thymus gland in the development and maintenance of the immune system is recognized. Biochemically characterized thymic extracts differentiate murine prethymic cells to functional T-lymphocytes. Thymosin fraction V differentiates prethymocytes to thymocytes, and mature thymocytes to competent T-lymphocytes. Thymopoietin and thymic humoral factor differentiate thymocytes; they have relatively little effect on prethymocytes. Serum thymic factor also affects a cell already at the thymocyte stage. The relative importance of each factor in the differentiation of T-lymphocytes remains unknown. Most likely, they act sequentially to produce a competent circulating T cell. The site of cellular differentiation in man by thymic factors is less well defined than in the murine system. It is established that thymosin fraction V, thymic humoral factor, and thymopoietin differentiate a subpopulation of isolated peripheral blood null lymphocytes (T cell rosette negative, surface immunoglobulin negative) to form T cell rosettes. In some situations, T cell function as assessed by response to allogeneic cells or plant lectins is enhanced following incubation with the factors. Peripheral blood lymphocytes isolated from subpopulations of children with primary or secondary immunodeficiency, or from adults with autoimmune disease or malignancy, have been incubated with thymosin fraction V. Enhanced T cell rosette formation has occurred in a subgroup of these patients. Notably, children with severe combined immunodeficiency and without stem cells for thymic factors to differentiate have had no increase in T cell rosette formation. The most important potential contribution of thymic factor research will be its precise application to the treatment of human disease. As our understanding of the differentiation of the human T cell approaches our understanding of the murine system, a more careful approach to the pathogenesis of human disease should be possible. Monoclonal antibodies capable of identifying human thymocyte and lymphocyte surface antigens have become available. By (1) evaluating the effect or effects of factors on normal human lymphocyte differentiation; (2) understanding the biochemical mechanism or mechanisms through which thymic factor differentiation occurs; (3) identifying specific abnormalities in individual disease entities; and (4) correlating disease pathogenesis with specific thymic factor effect, a logical approach to replacement therapy should be possible.