8 Thymic Hormones in Primary Immunodeficiency

Abstract

The central role of the thymus gland in the development and maintenance of the immune system is recognized. Biochemically characterized thymic extracts are capable of differentiating human prethymic cells. The precise mechanism of differentiation by thymic factors is poorly defined. Thymosin fraction 5, thymostimulin, thymic humoral factor, thymopoietin and TP5 differentiate a subpopulation of isolated peripheral blood null lymphocytes (T cell rosette negative, surface immunoglobulin negative) from humans to form T cell rosettes. Bone marrow stem cells, isolated both from normal individuals and from some patients with primary immunodeficiency disease, can be differentiated to HTLA-positive, T cell rosetteforming cells. In some situations, T cell function as assessed by response to allogeneic cells or plant lectins is increased after incubation with thymic factors. Peripheral blood lymphocytes isolated from some children with primary or secondary immunodeficiency disease or from adults with autoimmune disease or malignancy have been incubated with thymic factors. Enhanced T cell rosette formation has occurred in a subgroup of these patients. Notably, children with severe combined immunodeficiency without stem cells have not had increased T cell rosette formation. The most important potential contribution of thymic factor research will be its precise application to the treatment of disease in humans. The understanding of the differentiation of human T cells is increasing and will allow us to define the pathogenesis of immunodeficiency disease in the human. Eventually, correlating disease pathogenesis with specific thymic factor effect(s) should allow for a logical approach to replacement therapy.