Kwan Joanne, Killeen Nigel
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA.
J Immunol. 2004 Apr 1;172(7):3999-4007. doi: 10.4049/jimmunol.172.7.3999.
Developing thymocytes migrate from the cortex to the medulla of the thymus as a consequence of positive selection. This migration is likely to be essential for tolerance because it allows the developing cells to move into an environment that is optimal for negative selection. Guidance mechanisms that draw positively selected thymocytes into the medulla have not been clarified, but several studies have implicated chemokines in the process. CCR7, the receptor for the medullary chemokines CCL19 and CCL21, is induced on thymocytes during their positive selection. In this study we show that premature expression of CCR7 repositions CD4(+)CD8(+) double-positive cells into the medulla of transgenic mice. This repositioning of the thymocytes is accompanied by impairment of their development. The data show the involvement of CCR7 in medullary migration and emphasize the importance of proper thymocyte positioning for efficient T cell development.
在阳性选择的作用下，正在发育的胸腺细胞从胸腺皮质迁移至髓质。这种迁移对于免疫耐受可能至关重要，因为它能使发育中的细胞进入最适合阴性选择的环境。引导阳性选择的胸腺细胞进入髓质的机制尚不清楚，但多项研究表明趋化因子参与了这一过程。CCR7是髓质趋化因子CCL19和CCL21的受体，在胸腺细胞阳性选择过程中被诱导表达。在本研究中，我们发现CCR7的过早表达会使CD4(+)CD8(+)双阳性细胞重新定位到转基因小鼠的髓质中。胸腺细胞的这种重新定位伴随着其发育受损。数据表明CCR7参与了髓质迁移，并强调了胸腺细胞正确定位对于高效T细胞发育的重要性。
