Biochemistry of Thymic Factors

All of the thymic preparations that will be discussed in this chapter were first identified as crude thymic extracts with the ability to restore or enhance various parameters of thymic-dependent immunity either in vitro or in vivo by using lymphoid cells isolated from various immunodeficient animal models. Purified products were then isolated from the crude extracts and exhibited biologic effects similar to the crude preparations. The demonstrations that a number of biochemically unique thymic products exhibited similar biologic activities have been difficult to rationalize (cf. Stutman, 1983). In 

In this section we will review the biochemical and biologic properties of the well-characterized thymic preparations. It should be stressed that although many different thymic factors have been described that can induce T cell differentiation in vitro and/or in vivo in various experimental systems, very few have satisfied all of the requirements for categorization as true thymic hormones. Indeed, detailed thymectomy and thymus reimplantation studies to establish the absolute thymus dependency of circulating bioactivity have only been performed for thymulin (Bach et al., 1972 Bach and Dardenne, 1973). Although thymosin otj, thymosin P4, and thymopoietin are all detectable in serum, strict thymus dependency has not, at this time, been completely established. 

Thymosin fraction 5 (TF5) is a partially purified mixture of polypeptides prepared from calf thymus glands as starting material (Hooper et al., 1975). The crude thymus extract is purified by a heat step, acetone precipitation, and fractionation with ammonium sulfate. The 25%-50% ammonium sulfate precipitate is further subjected to ultrafiltration using an Amicon DC-2 hollow fiber system to yield fraction 5 that is lyophilized. Fraction 5 consists of 10 major and at least 30 minor polypeptides on analytical isoelectric gel focusing (Fig. 8), with molecular weights ranging from 1000 to 15,000, and is 

1981) (Fig. 8). TPg and TP4 appear to share an identical sequence through most of their amino-terminal part and differ in the carboxyl-terminal ends. With the use of immunofluorescent techniques and heterologous antisera to TPg and TP4, these peptides were found to localize almost exclusively to the subcapsular thymic epithelial cells covering the thymic cortex, and unlike Tttj, they were not present within thymic medullary epithelial cells (Hirokawaetfl/., 1982 Haynesef a/., 1983a,b,c Haynes, 1984). 

A radioimmunoassay for TP4 has been developed (see Section 7.2.1.2) and it has been identified in both animal and human sera at concentrations much higher than that of Taj (Naylor and Goldstein, 1984). However, TP4 does 

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