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Thymopoietin, a polypeptide hormone isolated from bovine thymus, induced in vitro the differentiation of prothymocytes to cells with the antigenic and functional characteristics of intrathymic thymocytes. These changes included the acquisition of the differentiation antigens TL and Thy-1 (theta) and the ability to respond to the mitogen Con-A. Thymopoietin appears to be highly speicfic in inducing the prothymocyte to be highly specific in inducing the prothymocyte to thymocyte differentiation and does not affect the pluripotential stem cell measured by the colony forming assay (CFU-S), the erythropoietin-sensitive cell or B-cells. Experiments are in progress to determine whether additional hormonal inductive signals are required to complete the differentiation of an immunologically competent T-cell.

The clinical manifestations in homozygous thalassemia may be attributed to the defect in hemoglobin synthesis (Figure 16). It is best typified by beta thalassemia, where excess alpha chains accumulate to form intracytoplasmic erythrocytic inclusions. This leads to anemia, bone marrow hyperplasia, osteoporosis, hemosiderosis, and organ failure.

The concept that has emerged from our experiments and those of others is that erythroid stem cells are committed to undergo a program of erythroid differentiation with respect to the ultimate hemoglobin phenotype of their progeny erythrocytes. A clear distinction can be drawn between the switch from Hb A (or Hb F) to Hb C in sheep and the switch from Hb F to adult hemoglobin in humans. The former appears to be regulated in a relatively late erythroid stem cell with characteristics of CFU-E. In contrast, the CFU-E found in adult sheep bone marrow from animals that lack the beta C gene appear to be preprogrammed to produce only adult hemoglobin. Fetal stem cells may be induced to synthesize Hb C within a time frame that is similar to that seen in cultures of adult bone marrow. Thus, a common mechanism modulating the potential for expression of this gene and commitment of erythroid stem cells with respect to Hb C production in progeny erythroblasts seems quite likely. Again fetal CFU-E and BFU-E in animals lacking the beta C gene appear to be, for the most part, committed toward producing erythroblasts making Hb F. Further analysis will be required to determine at exactly which stage of stem cell differentiation this programming occurs and also the factors that are important in modulating the potential for fetal and adult hemoglobin synthesis.