Biologic Activity of Thymic Factors

The concept that thymic hormones exist is now well accepted. However, many controversies still persist because of the multiplicity of different thymic products that have been isolated from thymus tissue over the past several decades. Many of the peptides appear to fulfill at least some of the accepted criteria for categorization as true thymic hormones. However, it is still unclear whether the various thymic polypeptides are components of a single thymic hormone (prohormone) that is capable of exhibiting the complete gamut of biologic properties ascribed to all of the different thymic peptides or whether each peptide alone or in certain combinations with other factors, at both intrathymic and extrathymic locations, regulates specific steps of T cell maturation. In this section we will review the biologic properties attributable to thymic factors in both animals and man. 

The nude mouse is the best experimental model for primary T cell immunodeficiency. This mutant strain has a congenital thymic aplasia resulting in absence of functional T cells and severely impaired immunity (De Sousa et al., 1969). Attempts to fully reconstitute such animals with thymic factors have been mostly unsuccessful, with the exception of one report (Ikehara et al., 1975). It is likely that lull immunologic reconstitution requires an intact thymus and development of progenitor T cells in the thymic microenvironment. 

Nevertheless, the influence of thymic factors on components of the immune response has still been analyzed by using this model. Thus, it has been shown that TP3 and Tp can induce expression of TdT in bone marrow and spleen cells from nude mice (Pazmino et al., 1978a,b) and that Toj can 

When a less severely immunocomprised host, that is, an adult thymec-tomized animal was used, it has been shown that suppressor cell activity can be restored with injections of thymosin or FTS and that phenotypic changes that occur in splenic T cells after thymectomy can be reversed by TP5 or FTS (Nash et al., 1981 Bach, 1977a). In an irradiated, thymectomized, and bone marrow-restored host, both bone marrow and spleen cells were induced with TF5 and Toj to provide helper cell activity for antibody production (Ahmed et al., 1979). 

In addition to inducing T cell antigens, TF5, TP3, TP4, and Taj have been shovra to induce the expression of TdT in normal mouse bone marrow cells. Of particular interest are studies demonstrating that only 50% of Lyt-1,2,3 induced cells are TdT , suggesting the existence of TdT and TdT+ T-cell precursors in bone marrow, the latter of which might give rise to a medullary thymocyte population (Goldschneider et al., 1981). 

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