Organogenesis of the thymus anlagen initiates in mice on day 11 of gestation (Teh 1993; Shortman et al. 1998) and derives from the 3rd and 4th pharyngeal pouches (Manley and Blackburn 2003). The thymus architecture is composed of both epithelial and mesenchymal cell components, both of which contribute to the selection of functional thymocytes during development (Manley and Blackburn 2003). The thymus is immediately colonized by immigrant HSC, which are detectable by gestational day 11 (Auerbach 1961; Rodewald and Fehling 1998). Hematopoietic cells in the thymus on day 11 are ckit+, Thy-1-, CD3-, CD4-, CD8-, CD25-, a phenotype characteristic of uncommitted HSC (Peault et al. 1994). However, by day 13, the majority of thymic hematopoietic cells have begun to express Thy-1, CD3, CD4, and CD8, cell surface antigens more closely associated with T lymphocyte devel-
opment (Rodewald and Fehling 1998). Hematopoiesis in the developing thymus is largely limited to lymphocyte production; however, HSC continue to be detectable in this organ throughout gestation and retain the capacity to form all blood cell lineages when transplanted.
Although less is known about the role of cytokines in fetal T cell development than about B lymphopoiesis, immature proliferating thymocytes form colonies in vitro when exposed to the proliferative cytokines IL-7 and ckit-ligand (CFU-IL-7) (Namen et al. 1998; Lee et al. 1989; Moore et al. 1996) and it is likely that both of these cytokines play a key role during in utero T cell development. Developing thymic lymphocytes initiate expression of the T-cell receptor (TcR) within the thymic cortex and then undergo sequential interactions with epithelial and mesodermal-derived stromal cells which result in selection to delete nonreactive and autoreactive cells (Cosgrove et al. 1992). Soon after birth in rodents, T lymphocytes with characteristic expression of the full complement of TcR-associated molecules are found in peripheral lymphoid organs, including the spleen (Rodewald and Fehling 1998).
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