Cytokine gene expression in murine fetal intestine: potential for extrathymic T cell development

An increasing body of evidence suggests that certain T cell subsets mature extrathymically in the epithelium of the intestine. In the studies reported here, the authors have analysed cytokine/growth factor gene expression, recombinase-activating gene RAG-1 and RAG-2 gene expression and terminal deoxynucleotidyl transferase (TdT) gene expression in mouse fetal intestine and fetal thymus and liver, two known haematopoietic tissues. Stem cell factor (SCF) and interleukin 7 (IL-7) message was abundant in all three tissues during fetal development. IL-2 and IL-4 were not expressed in fetal gut but IL-4 was weakly detected in fetal liver and thymus. IL-9 and IL-13 mRNA was detected in all fetal tissues and IL-15 mRNA was abundant in fetal intestine but only weakly expressed in fetal liver and thymus. mRNA for SCF, IL-7, IL-13 and IL-15 was also detected in fibroblast-like cell lines derived from fetal intestine. RAG-1 and RAG-2 mRNA was detected in all three fetal tissues. TdT mRNA was not detected in fetal gut or liver but was weakly expressed in (fetal day) fd19-20 fetal thymus. Long-term (> 6 weeks) in vitro growth of IEL was achieved by coculturing intraepithelial lymphocytes (IEL) with IL-7-secreting fibroblasts in the presence of SCF and IL-2. The data show that the fetal mouse gut provides a suitable environment for lymphocyte development and receptor rearrangement, similar to fetal thymus and liver, even though expansion of intestinal IEL is delayed until 2-3 weeks after birth.