Haematopoietic cell lines capable of colonizing the thymus following in vivo transfer expressed T-cell receptor gamma-gene immature mRNA.

To clarify the mechanism by which progenitor T (pro-T) cells recognize and enter the thymus, an attempt was made to produce haematopoietic cell lines by the fusion of BALB/c nude mouse bone marrow or foetal liver cells (gestation 14 and 15 days) with AKR thymoma BW5147, thereby immortalizing cells with potency to colonize the thymus, a characteristic of pro-T cells rarely found in adult bone marrow or foetal liver. The hybridomas thus produced were classified according to the phenotype of surface markers, T-cell receptor (TcR) gene configuration and expression. All hybridomas were negative in the surface expression of T-cell markers such as TcR alpha beta, TcR gamma delta, CD3, CD4 and CD8. They had TcR beta-, gamma- and delta-genes, each with a different status with respect to configuration and transcription. Some possessed partially rearranged TcR genes and others expressed immature TcR mRNA. The cell lines were examined for their capacity to colonize the thymus following intravenous injection into recipient mice. It was found that the cells with capacity of colonizing the thymus expressed immature TcR delta mRNA, while the cell lines lacking TcR delta-genes did not home to the thymus. These findings imply that the potency for migrating to thymus is closely associated with the particular stage of prethymic cell differentiation which could be estimated by the analysis of TcR genes, and that some cell lines with the expression of TcR delta-gene mRNA and the ability to colonize the thymus are derived from pro-T cells.