丙酮酸激酶M2缺失不影响TCRαβ^+T细胞的增殖、活化、分化和抗肿瘤能力

PKM2 is dispensable for the proliferation,activation,differentiation and antitumor capacity of TCRαβ^+T cells

为探究丙酮酸激酶M2(pyruvate kinase M2,PKM2)在TCRαβ^+T细胞中的功能,研究制备了TCRαβ^+T细胞条件性敲除PKM2小鼠。FACS检测发现PKM2缺失不影响小鼠外周淋巴器官中TCRαβ^+CD4^+与CD8^+T细胞百分比、增殖能力及活化潜能。TCRαβ^+T细胞特异性PKM2^-/-小鼠可在结肠组织中形成正常的Th1与Th17亚群,也可在体内外诱导产生正常的Th1与Th17。PKM2缺失同样不影响MC38移植瘤生长,也不改变移植瘤中TCRαβ^+CD4^+/CD8^+T细胞比例和T细胞IFN-γ的表达。因而,TCRαβ^+T细胞特异性PKM2^-/-小鼠具有正常的T细胞功能亚群。Western blotting表明,PKM2^-/-TCRαβ^+CD4^+与CD8^+T细胞中PKM1表达上调。据此,作者推测PKM1部分代偿了PKM2在TCRαβ^+T细胞中的生理功能。

To study the functional role of PKM2 in TCRαβ^+T cells,we established a mouse strain with conditional knockout of PKM2 in TCRαβ^+T cells.FACS analysis demonstrated that PKM2 deficiency did not interfere cell frequency,proliferation and activation potential of TCRαβ^+CD4^+and CD8^+T cells in mouse peripheral lymphoid organs.Th1 and Th17 subsets of TCRαβ^+T cell-specific PKM2 knockout mice were normally developed in colon and naturally differentiated both in vitro and in vivo.PKM2 deletion did not affect the growth of tumor graft using MC38 cell line,the ratio of TCRαβ^+CD4^+relative to CD8^+T cells and their IFN-γexpression in tumor.Hence,TCRαβ^+T cell-specific PKM2 knockout mice have normal functional subsets of T cells.Western blotting revealed that PKM1 was upregulated in PKM2 deficient TCRαβ^+CD4^+and CD8^+T cells.Therefore,we infer that upregulation of PKM1 compensates part of the physiological function of PKM2 in TCRαβ^+T cells.