Transgenic expression of cyclin D1 in thymic epithelial precursors promotes epithelial and T cell development.
We previously reported that precursors within the keratin (K) 8+5+ thymic epithelial cell (TEC) subset generate the major cortical K8+5- TEC population in a process dependent on T lineage commitment. This report demonstrates that expression of a cyclin D1 transgene in K8+5+ TECs expands this subset and promotes TEC and thymocyte development. Cyclin D1 transgene expression is not sufficient to induce TEC differentiation in the absence of T lineage-committed thymocytes because TECs from both hCD3epsilon transgenic and hCD3epsilon/cyclin D1 double transgenic mice remain blocked at the K8+5+ maturation stage. However, enforced cyclin D1 expression does expand the developmental window during which K8+5+ cells can differentiate in response to normal hemopoietic precursors. Thus, enhancement of thymic function may be achieved by manipulating the growth and/or survival of TEC precursors within the K8+5+ subset.
Klug
D B
DB
Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, TX 78957, USA.
Crouch
E
E
Carter
C
C
Coghlan
L
L
Conti
C J
CJ
Richie
E R
ER
D000818:Animals; D017252:CD3 Complex; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D007633:Keratins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D019076:Transgenes
D017252:CD3 Complex; C115335:CD3E protein, human; D011948:Receptors, Antigen, T-Cell; D019938:Cyclin D1; D007633:Keratins