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After incubation with thymosin, a thymic hormone, normal bone marrow rosette-forming cells acquire T-cell characteristics, including increased sensitivity to azathioprine, anti-lymphocyte serum, and anti-theta serum. This activity of thymosin provides a new sensitive and reproducible bioassay for thymosin, and is well correlated with an in vivo graft-versus-host assay. In addition, incubation of spleen cells from adult thymectomized mice with thymosin in vitro restores to normal their diminished sensitivity to azathioprine and anti-lymphocte serum.

Cells with the ability to recognize self antigens have been demonstrated in the thymus of the neonatal mouse. The detection of these cells is based upon a newly described in vitro phenomenon termed the isogeneic lymphocyte interaction. This interaction is demonstrable by [(14)C]thymidine uptake in cultures containing mixtures of neonatal thymus cells and adult spleen cells from the CBA strain of mice. The response observed in these mixtures has been shown to be almost entirely due to thymic cell proliferation. Other isogeneic lymphoid cells cannot replace adult spleen cells. Thymic isogeneic lymphocyte interaction activity increases sharply after birth, begins to decline within the first week of life and is lost by adulthood. It is suggested that the isogeneic lymphocyte interaction may represent an in vitro model for cognitory and discriminatory cellular events occurring routinely in vivo.

The development of resistance to progressive tumor growth and the effect of a thymic extract upon this developmental process were examined in CBA/Wh mice. Inoculating mice of various ages with murine sarcoma virus (Moloney) permitted the assessment of the period of time postnatally at which the animals developed a threshold level of resistance to progressive tumor growth. Resistance in CBA/Wh mice, at the virus dose used, was first detected at approximately two weeks of age and was completely developed at five weeks.Thymosin, a soluble calf thymic fraction, when administered to neonatal mice beginning on the second day of life, significantly accelerated the rate of development of resistance to progressive tumor growth. The data suggest a humoral role for the thymus in the development of tumor immunity, and that the normal development of cell-mediated immunological competence can be accelerated through the use of thymus-derived extracts.

The purification and chemical properties of thymosin, obtained from bovine thymus tissue, are described. The biological activity of the thymic hormone has been assessed by a newly developed rosette assay, which permits measurement of thymus-dependent lymphoid cells. Thymosin activity is associated with a physico-chemically homogeneous protein of molecular weight 12,600. The hormonal activity is evident in in vitro incubation assay, after injection into adult thymectomized mice, and in prolonging survival of neonatally thymectomized mice and the reconstitution of their response to a skin allograft.