Analysis of cytokine gene expression during fetal thymic ontogeny using the polymerase chain reaction

The expression of 12 cytokine and cytokine receptor genes during mouse thymic ontogeny has been studied using the polymerase chain reaction. The data reveal that IL-2 gene transcription does not begin in the thymus until fetal day (Fd) 16. However, IL-2R beta-chain mRNA was detectable throughout the period of investigation, from Fd 14 to 20. This suggests that the potential for high or intermediate affinity IL-2 binding is present in the thymus before the IL-2 gene is actually expressed. Overall, cytokine gene induction occurred in two distinct patterns. In the first group, represented by IL-1 beta, IL-4, IL-5, IL-6, IL-7, IFN-gamma, and lymphotoxin (lymphotoxin or TNF-beta) there was detectable mRNA present from Fd 14 to 20. IL-1 alpha, IL-2, IL-3, and GM-CSF followed a second pattern in which gene induction was delayed until Fd 16. The expression of IL-7 and IL-2 genes showed an interesting temporal relationship. IL-7 mRNA transcription occurred before IL-2 but diminished from Fd 16 after the onset of IL-2 gene induction. Because these data reflect the in vivo progression of gene expression during T cell ontogeny, they provide a guideline for assessing the physiologic significance of thymocyte responses to cytokines at different stages of fetal development.