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.
Porcellini
S
S
Dipartimento di Biologia e Genetica per le Scienze Mediche, Università di Milano at Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute (HSR), Milano, Italy.
Panigada
M
M
Grassi
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D017252:CD3 Complex / Q000378:metabolism; D002450:Cell Communication; D002453:Cell Cycle; D016207:Cytokines / Q000235:genetics; D004254:DNA Nucleotidyltransferases / Q000172:deficiency*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D019426:Integrases; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D045522:Recombinases; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000201:enzymology* / Q000254:growth & development* / Q000276:immunology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D017931:DNA Primers; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D045522:Recombinases; C064655:V(D)J recombination activating protein 2; D004254:DNA Nucleotidyltransferases; D019426:Integrases; C115006:integron integrase IntI1