p18INK4C属于细胞周期蛋白激酶抑制剂,其突变或缺失与某些肿瘤的发生密切相关,如T细胞白血病,但目前关于p18调控T细胞发育及功能的研究还鲜有报道,其调控机制仍不明确.本研究利用p18基因敲除(p18KO)小鼠,系统地研究了胸腺中T细胞的早期发育及成熟T细胞的增殖和活化功能,并利用逆转录病毒的方法在Lin?造血干祖细胞上过表达p18,移植4个月后检测其对T细胞的影响.结果表明,p18的缺失对胸腺T细胞的早期发育影响不明显,但随着p18KO小鼠周龄的增加会促进CD4+CD8+双阳性T细胞的数量,此外,p18还通过影响CD3+成熟T细胞的细胞周期进程及IFN-?,GATA3,Tbx21和Foxp3等的表达增强脾脏T细胞的增殖和活化;进一步在造血干祖细胞上过表达p18后会影响T细胞的发育和成熟,进而纠正T细胞在数量上的异常.本研究阐释了p18在T细胞早期发育及后期活化中的调控机制,并证实可通过在干祖细胞水平改变p18的表达进而影响T细胞的分化,这对p18调控T细胞功能异常及参与T细胞白血病的发生提供了新的理论依据和重要的研究价值. p18INK4C is a cyclin kinase inhibitor, and its mutation or deletion is closely related to the occurrence of some tumors, such as T cell leukemia. However, little is known about the research on the function and the development of p18 regulatory T cells. The regulatory mechanism remains unclear In this study, p18 knockout (p18KO) mice were used to systematically investigate the early development of T cells in thymus and the proliferation and activation of mature T cells. The retroviral method was used to detect the expression of T lymphocytes on Lin? Hematopoietic stem / progenitor cells Overexpression of p18 and its effect on T cells after 4 months transplantation showed that the deletion of p18 had no obvious effect on the early development of thymus T cells but increased the percentage of CD4 + CD8 + In addition, p18 also enhances the proliferation and activation of splenic T lymphocytes by affecting the cell cycle progression of CD3 + mature T cells and the expression of IFN - ?, GATA3, Tbx21 and Foxp3; further, The expression of p18 will affect the development and maturation of T cells and thus correct the number of abnormal T cells.This study illustrates the regulatory mechanism of p18 in the early development and post-activation of T cells, The level of p18 changes in turn affect the T cell differentiation, which p18 regulatory T cell dysfunction and participate in the occurrence of T-cell leukemia provides a new theoretical basis and important research value.