![]() RAG-2−/− mice do not generate mature T cells and therefore the RAG-2−/− thymus is devoid of organized medullary regions. Analysis of the thymic stromal compartment reveals that progression through β-selection renders thymocytes competent to alter the pattern of IL-7 expression in the cortical TEC compartment. Intraperitoneal injection of Recombination Activating Gene deficient mice (RAG-2−/−) with anti-CD3&epsiv monoclonal antibody (mAb) induces CD4− 8− double negative thymocytes to undergo β-selection and differentiate into CD4+8+ cells. Furthermore, distinct thymocyte subsets regulate the expression of IL-7 and keratin 5 in adult cortical epithelium. However, thymocyte-derived signals play an essential role in regulating IL-7 expression in the adult TEC compartment. By analyzing mouse strains that sustain blocks at different stages of thymocyte development, we show that IL-7 expression is initiated independently of hematopoietic-derived signals during thymic organogenesis. Whereas IL-7 expressing TECs are present throughout the early thymic rudiment, the majority of IL-7 producing TECs are concentrated in the adult thymic medulla. Marked changes occur in the localization and regulation of IL-7 expressing TECs during development. IL-7 expression is initiated in the thymic fated domain of the thymic primordium by embryonic day 11.5, in a Foxn1 independent pathway. We have identified IL-7 expressing TECs throughout ontogeny and in the adult thymus by in situ hybridization analysis. TECs produce interleukin-7 (IL-7), a non-redundant cytokine that promotes the survival, differentiation, and proliferation of thymocytes. Concurrently, proper TEC differentiation in the adult thymus relies on thymocyte-derived signals. Epithelial cells in the thymus are organized in a three-dimensional network that provides support and signals for thymocyte maturation. T cell development is a multistage process of differentiation that depends on proper thymocyte-thymic epithelial cell (TEC) interactions. Ontogeny and regulation of interleukin-7 expressing thymic epithelial cells
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