Analysis by in situ hybridization of cells expressing mRNA for tumor-necrosis factor in the developing thymus of mice.

We have used in situ hybridization to investigate the expression of TNF-alpha genes by thymic cells during fetal development in mice. In 14-day-old fetal thymuses, very scarce cells produce TNF-alpha mRNA. A second phase of cytokine gene expression starts on day 16. The density of positive cells progressively increases up to day 20. Thymuses at 15 days of gestation and after birth do not express detectable cytokine mRNA. In an attempt to identify the nature of the TNF-alpha mRNA-producing cells, acid phosphatase activity, which is characteristic of the macrophage lineage, was studied in the same thymuses. Acid phosphatase-positive cells only appear on day 15. Their frequency increases up to birth. However, no correlation can be established between acid phosphatase--and TNF alpha mRNA--positive cells. The results indicate that a small subset of thymic cells is responsible for TNF-alpha mRNA production during ontogeny: These cells are not yet identified. The possible role of TNF-alpha in thymic ontogeny is discussed.