Molecular and cellular aspects of induced thymus development in recombinase-deficient mice.

Thymus development and microenvironment organization require stage- and site-specific cross-talk between thymocyte and stroma. In this study we have used recombinase-activating gene-deficient (RAG-2(-/-)) mice to analyze regulated gene expression both in thymocytes and stromal cells following injection of anti-CD3 monoclonal antibodies as inducer of thymus development. We show that IFN-gamma, TNF-alpha and lymphotactin are transcriptionally regulated in thymocytes, whereas cytoskeletal keratin 14, IL-1alpha and TNF-alpha are regulated in the stroma, quantitatively reproducing the variations associated with beta selection of thymocytes. In addition, RAG-2(-/-) thymus development is associated with entry of epithelial cells into the cell cycle. The histochemical evidence that expanded RAG-2(-/-) thymus becomes undistinguishable from wild-type cortex further suggests that cross-talk phenomena occurring during beta selection of thymocyte are reproduced in this system.