Studies on chemokines and chemokine receptors concerning migration of T-progenitor cells into the thymus anlagen

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1)We report the existence of a second thymus in the neck, which develops after birth, reaching size of a small lymph node. The cervical thymus displayed a typical cortex-medulla structure, and found to be functional with regards to T cell development, and correct T cell deficiency in athymic nude mice. (Science 312, 284. 2006).2)We showed migration of T progenitor cells into the thymus anlages occurs normally in CXCL12 mutant mice on embryonic day 11-12 comparable to that of normal littermates. However, the number of Double Negative cells in the thymus of CXCL12 mutant mice is small as compared with those of control mice. Therefore, CXCL12 do not regulate T progenitor cell migration into the thymus but proliferation of early thymocytes. (J.Immunol. 170, 4649. 2003)3)In normal mice, endothelial precursor cells (VEcadherin+ and Flk1+) and endothelial cells (CD31+) accumulate in mesenchymal layer of the thymus anlage on Ed11-12, and migrate among the epithelial cluster of the thymus anlag … More e on Ed12-13 and form tube structure on Ed13 and thereafter. PDGFRbeta positive mesenchymal cells also migrate in the vicinity of endothelial cells among epithelial cells of the thymus anlage on Ed13. Neither endothelial precursor cells nor endothelial cells are accumulated in mesenchymal layer of the nude thymus anlage, and consequently blood vessels are not formed in the nude thymus anlage. VEGF positive epithelial cells are detected in the normal thymus anlage on Ed12-13, but not in the nude thymus anlage. It is suggested that development of thymic epithelial cells to produce VEGF, which could be controlled by the expression of Foxn1 gene, triggers vascularization of the thymus anlages. (Submitted)4)The earliest thymic migrant cells, which express CD117 and IL7R, are identified as progenitor cells restricted to T/NK/DC lineages. (J.Immunol. 174, 2525. 2005)5)A polycomb gene, Mel-18 regulates early T cell development in the thymus through maintenance of Hes-1 expression in developing thymocytes. (J.Immunol. 174, 2507. 2005)6)The perivascular spaces (PVS) of the thymus in mice distribute in the corticomedullary junction surrounding large blood vessels. Our results indicate that the PVS is a transit pathway for progenitor cells to immigrate into the thymus, and for mature T cells to emigrate out from the thymus. (Submitted) Less