CD71+TER119+红系前体细胞对新生儿T淋巴细胞免疫应答的影响和机制研究

Previous studies show that the decreased level of T cell immune response in neonatal mice is mainly due to the immature of the immune cells. However, the microenvironment of T cell immune responses in the secondary lymphoid organs (SLOs) of neonatal mice has been rarely investigated. Our preliminary results show that the expression level of CCL19 and CCL21 in SLOs of neonatal mice was significantly lower than that in adult mice, and the expression level of CCL19 and CCL21 was increased gradually with maturation of neonatal mice. More important, the proportion of CD71+TER119+ erythroid progenitor cells was significantly increased in the SLOs of neonatal mice, and decreased according to the maturation of neonatal mice, which was negatively correlated with the expression level of CCL19 and CCL21 in SLOs. We speculate that the accumulation of CD71+TER119+ erythroid progenitor cells in secondary lymphoid organs of neonatal mice would inhibit the secretion of chemokines CCL21 and CCL19 from stromal cells, and further interfere with the homing-to-SLOs ability of T cells, and inhibit T cells immune response. This project will help to explore the effect of accumulation of CD71+TER119+ erythroid progenitor cells in neonatal mice on the homing-to-SLOs ability of T cells and T cells immune response as well as the molecular mechanism.

以往研究表明新生儿的T细胞免疫应答水平低下主要是由于其免疫细胞尚未发育成熟造成的；但新生小鼠二级淋巴器官免疫微环境的改变对T细胞免疫应答的影响则未见报道。我们的结果表明，新生小鼠二级淋巴器官中T细胞趋化因子CCL19和CCL21的表达水平显著低于成年小鼠，且CCL19和CCL21的表达随着新生小鼠周龄的增加逐渐升高，此外新生小鼠脾脏中的CD71+TER119+的红系前体细胞显著增多，且随着小鼠周龄的增加逐渐减少，这与CCL21和CCL19的表达呈负相关。我们推测新生小鼠二级淋巴器官脾脏中显著增多的CD71+TER119+的红系前体细胞可以通过抑制二级淋巴器官中CCL21、CCL19的分泌，削弱T细胞的归巢能力，从而影响T淋巴细胞的免疫应答。本项目拟在前期实验的基础上深入阐明新生小鼠二级淋巴器官中CD71+TER119+细胞显著增多对T细胞免疫应答的影响的具体分子机制。

以往研究表明新生儿的T细胞免疫应答水平低下主要是由于其免疫细胞尚未发育成熟造成的；但新生小鼠二级淋巴器官免疫微环境的改变对T细胞免疫应答的影响则未见报道。我们的结果表明，新生小鼠二级淋巴器官中T细胞趋化因子CCL19和CCL21的表达水平显著低于成年小鼠，且CCL19和CCL21的表达随着新生小鼠周龄的增加逐渐升高，此外新生小鼠脾脏中的CD71+TER119+的红系前体细胞显著增多，且随着小鼠周龄的增加逐渐减少，这与CCL21和CCL19的表达呈负相关。进一步研究发现新生小鼠二级淋巴器官脾脏中显著增多的CD71+TER119+的红系前体细胞可以通过抑制二级淋巴器官中CCL21、CCL19的分泌，削弱T细胞的归巢能力，从而影响T淋巴细胞的免疫应答。本项目深入阐明了新生小鼠二级淋巴器官中CD71+TER119+细胞显著增多对T细胞免疫应答的影响的具体分子机制。