%0 Journal Article
%T Stage-specific changes in fetal thymocyte proliferation during the CD4-8- to CD4+8+ transition in wild type, Rag1-/-, and Hoxa3,Pax1 mutant mice
%A Dong-ming Su
%A Nancy R Manley
%J BMC Immunology
%D 2002
%I BioMed Central
%R 10.1186/1471-2172-3-12
%X Wild type fetal and adult thymus showed stage-specific differences in the proliferation profiles of developing thymocytes, with fetal stages showing generally higher levels of proliferation. The proliferation profile of fetal thymocytes from Rag1-/- mutants also had stage-specific increases in proliferation compared to wild type fetal thymocytes, in contrast to the lower proliferation previously reported for thymocytes from adult Rag1-/- mutants. We have previously shown that Hoxa3+/-Pax1-/- mice have abnormal fetal TEC development, resulting in increased apoptosis at the TN to DP transition and decreased DP cell numbers. Fetal thymocytes from Hoxa3+/-Pax1-/- compound mutants had increased proliferation, but fewer proliferating cells, at the DP stage. We also observed a decrease in the level of the cytokines IL-7 and SCF produced by Hoxa3+/-Pax1-/-TECs.Our results indicate complex and stage-specific effects of abnormal TEC development on thymocyte proliferation.Thymocyte development occurs within a complex network of cells, extracellular matrix, and secreted factors referred to as the thymic microenvironment [1]. Current evidence suggests that this microenvironment is created during fetal thymus organogenesis through stage-dependent interactions between differentiating thymic epithelial cells (TECs) and developing thymocytes [2-6]. Therefore, blocks at different stages of thymocyte development result in differential effects on TEC differentiation and function. Because of the complex interdependence of TEC and thymocyte differentiation, defects in fetal TEC development can be caused either directly by cell-autonomous TEC differentiation defects, or indirectly by defective thymocyte maturation. Once a mature thymic environment is formed, many, if not all stages of thymocyte maturation require interactions with thymic epithelial cells. Therefore, defects in TECs can in turn cause defects in thymocyte differentiation, proliferation, or cell death.Thymocyte differentiati
%U http://www.biomedcentral.com/1471-2172/3/12