Kim C H, Pelus L M, White J R, Broxmeyer H E
Department of Microbiology/Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Blood. 1998 Jun 15;91(12):4434-43.
Differentiation-dependent thymocyte migration in the thymus may be important for T lymphopoiesis and might be regulated by thymic chemoattractants. We examined modulation of chemotactic responsiveness of thymocyte subsets during their early to late stages of development in response to 2 thymus-expressed chemokines, SDF-1 and CKbeta-11/MIP-3beta/ELC. SDF-1 shows chemotactic preference for immature thymocytes (subsets of triple negative thymocytes and double positive [DP] subset) over mature single positive (SP) thymocytes. CKbeta-11/MIP-3beta/ELC shows low chemotactic activity on the immature thymocytes, but it strongly attracts mature SP thymocytes, effects opposite to that of SDF-1. SDF-1-dependent chemoattraction of immature thymocytes is not significantly desensitized by a negative concentration gradient of CKbeta-11/MIP-3beta/ELC, and chemoattraction of mature SP thymocytes to CKbeta-11/MIP-3beta/ELC is not antagonized by SDF-1, demonstrating that these two chemokines have different chemoattractant preferences for thymocyte subsets and would probably not inhibit each other's chemotaxis in the event of microenvironmental coexpression. The chemotactic responsiveness of thymocytes and mature T cells to the 2 chemokines is respectively enhanced after selection process and migration to the spleen. These studies demonstrate the presence of thymocyte chemoattractants with differential chemotactic preference for thymocytes, a possible mechanism for thymocyte migration in the thymus.
胸腺中依赖分化的胸腺细胞迁移对于T淋巴细胞生成可能很重要,并且可能受胸腺趋化因子调控。我们检测了胸腺细胞亚群在发育早期至晚期对两种胸腺表达的趋化因子SDF-1和CKbeta-11/MIP-3beta/ELC的趋化反应性的调节。SDF-1对未成熟胸腺细胞(三阴性胸腺细胞亚群和双阳性[DP]亚群)的趋化作用优于成熟的单阳性(SP)胸腺细胞。CKbeta-11/MIP-3beta/ELC对未成熟胸腺细胞的趋化活性较低,但它强烈吸引成熟的SP胸腺细胞,其作用与SDF-1相反。CKbeta-11/MIP-3beta/ELC的负浓度梯度不会使未成熟胸腺细胞对SDF-1的依赖趋化作用显著脱敏,SDF-1也不会拮抗成熟SP胸腺细胞对CKbeta-11/MIP-3beta/ELC的趋化作用,这表明这两种趋化因子对胸腺细胞亚群具有不同的趋化偏好,并且在微环境共表达的情况下可能不会相互抑制趋化作用。胸腺细胞和成熟T细胞对这两种趋化因子的趋化反应性在选择过程和迁移至脾脏后分别增强。这些研究证明了存在对胸腺细胞具有不同趋化偏好的胸腺细胞趋化因子,这是胸腺中胸腺细胞迁移的一种可能机制。