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

与 T 祖细胞迁移至胸腺原基有关的趋化因子和趋化因子受体的研究

基本信息

批准号：
14570288
负责人：
AMAGAI Takashi
金额：
$ 2.18万
依托单位：
Meiji University of Oriental Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2005
项目状态：
已结题

项目摘要

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

1）我们报告了在颈部存在第二个胸腺，它在出生后发育，达到一个小淋巴结的大小。颈部胸腺显示出典型的皮质-髓质结构，并且发现其在T细胞发育方面具有功能，并且在无胸腺裸鼠中纠正T细胞缺陷。（《科学》，312，284页。2006）。2）我们显示T祖细胞向胸腺原基的迁移在胚胎第11-12天的CXCL 12突变小鼠中正常发生，与正常同窝出生的小鼠相当。然而，与对照小鼠相比，CXCL 12突变小鼠胸腺中的双阴性细胞数量较少。因此，CXCL 12不调节T祖细胞向胸腺的迁移，而是调节早期胸腺细胞的增殖。（J.Immunol.170，4649. 3）在正常小鼠中，内皮前体细胞（VE cadherin+和Flk 1+）和内皮细胞（CD 31+）在Ed 11 -12时聚集在胸腺原基的间充质层中，并在胸腺的上皮簇之间迁移， ...更多信息在Ed 12 -13形成e，在Ed 13及以后形成管状结构。在Ed 13，PDGFR β阳性间充质细胞也迁移到胸腺原基上皮细胞中的内皮细胞附近。内皮前体细胞和内皮细胞均未聚集在裸胸腺原基间充质层，因此裸胸腺原基中不形成血管。在Ed 12 -13的正常胸腺原基中检测到VEGF阳性上皮细胞，而在裸胸腺原基中未检测到。提示胸腺上皮细胞的发育产生VEGF，并受Foxn 1基因表达的调控，触发了胸腺原基的血管化。（已提交）4）表达CD 117和IL 7 R的最早的胸腺移行细胞被鉴定为仅限于T/NK/DC谱系的祖细胞。（J.Immunol.174，2525. 5）多梳基因Mel-18通过维持发育中的胸腺细胞中的Hes-1表达来调节胸腺中的早期T细胞发育。（J.Immunol.174，2507. 2005)6)小鼠胸腺血管周围间隙（PVS）分布于大血管周围的皮髓质交界处。我们的研究结果表明，PVS是一个过境通道祖细胞迁移到胸腺，成熟T细胞从胸腺迁出。（已提交）减