Abstract
We have used in situ hybridization to investigate the expression of TNF-α genes by thymic cells during fetal development in mice. In 14-day-old fetal thymuses, very scarce cells produce TNF-α 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-α 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 TNFα mRNA— positive cells. The results indicate that a small subset of thymic cells is responsible for TNF-α mRNA production during ontogeny: These cells are not yet identified. The possible role of TNF-α in thymic ontogeny is discussed.
Highlights
A central issue of T-cll ontogeny is the identification of the signals and growth factors required for the proliferation and differentiation of immature cells in the thymus
We explored the TNF-o mRNA-producing capacity of fetal thymuses
In an attempt to identify the cells responsible for this TNF-o production, we looked for acid phosphatase activity, which is a good marker of thymic macrophages (Duijvestijn et al, 1983)
Summary
A central issue of T-cll ontogeny is the identification of the signals and growth factors required for the proliferation and differentiation of immature cells in the thymus. TNF-o can induce a number of negative and positive regulators of cell growth [e.g., granulocyte-macrophage CSF (Munker et al, 1986), IL-1 (Nawroth et al, 1986), IFN-fl (Kohase et al, 1986)] in a variety of .cell types. These latter observations suggest that TNF-o may be involved in the control of cell proliferation and differentiation. Several experimental data suggest that TNF-o may play a role in thymic lymphopoiesis It stimulates thymocyte proliferation in vitro in association with other cytokines: It synergizes with IL-2 and IL-7 on the CD4-CD8- double-
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