Enhanced T cell proliferation in mice lacking the p85β subunit of phosphoinositide 3-kinase
Enhanced T cell proliferation in mice lacking the p85β subunit of phosphoinositide 3-kinase
复制标题
DOI：
10.4049/jimmunol.172.11.6615
复制
发表时间：
2004-06-01
影响因子：
4.4
通讯作者：
Fruman, DA
中科院分区：
文献类型：
--
作者：
Deane, JA;Trifilo, MJ;Fruman, DA
磷酸肌醇3-激酶激活对淋巴细胞增殖和存活是重要的。破坏编码主要磷酸肌醇3-激酶调节亚型p85 α的基因会损害B细胞的发育和增殖。然而，在p85 α不存在的情况下，T细胞功能是完整的。在这项研究中，我们测试的假设，相关的亚型p85 β是一个必要的调节亚基的T细胞信号。出乎意料的是，当用抗CD 3加IL-2刺激时，缺乏p85 β的T细胞显示出增殖的显著增加和死亡的减少。CD 4（+）和CD 8（+）T细胞都完成了更多的细胞分裂。转录谱显示p85 β缺陷T细胞中caspase-6 mRNA水平降低，这是由caspase-6酶活性降低引起的。用小鼠肝炎病毒感染p85 β缺陷小鼠后，体内也观察到T细胞蓄积增加。总之，这些结果表明p85 β在限制T细胞扩增中的独特作用。
Phosphoinositide 3-kinase activation is important for lymphocyte proliferation and survival. Disrupting the gene that encodes the major phosphoinositide 3-kinase regulatory isoform p85alpha impairs B cell development and proliferation. However, T cell functions are intact in the absence of p85alpha. In this study, we test the hypothesis that the related isoform p85beta is an essential regulatory subunit for T cell signaling. Unexpectedly, T cells lacking p85beta showed a marked increase in proliferation and decreased death when stimulated with anti-CD3 plus IL-2. Both CD4(+) and CD8(+) T cells completed more cell divisions. Transcriptional profiling revealed reduced levels of caspase-6 mRNA in p85beta-deficient T cells, which was paralleled by reduced caspase-6 enzyme activity. Increased T cell accumulation was also observed in vivo following infection of p85beta-deficient mice with mouse hepatitis virus. Together, these results suggest a unique role for p85beta in limiting T cell expansion.