Bosque Alberto, Marzo Isabel, Naval Javier, Anel Alberto
Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza E-50009, Spain.
Mol Immunol. 2007 Feb;44(6):1446-53. doi: 10.1016/j.molimm.2006.04.029. Epub 2006 Jun 27.
The mechanisms responsible for the down-modulation of the activation of separated CD4(+) or CD8(+) human T cell blasts were studied using cells obtained from healthy donors. In the absence of IL-2, human CD4(+) T cell blasts were sensitive to both FasL and Apo2L/TRAIL, but human CD8(+) T cell blasts died, with no additional effect of death receptor ligation. CD8(+) T cell blasts were more sensitive than CD4(+) T cell blasts to apoptosis induction by IL-2 deprivation, which was associated with a decrease in the expression of anti-apoptotic proteins of the Bcl-2 family, especially of Mcl-1 in CD8(+) T cell blasts. The maintenance of high levels of Bim expression was also necessary, since down-modulation of Bim expression by siRNA in normal human CD8(+) T cell blasts greatly reduced apoptosis by IL-2 deprivation. These data, together with previous works, point to an important role of the presence or absence of immuno-stimulatory cytokines in the type of regulation of human CD8(+) T cell responses (death by cytokine deprivation versus death receptor inhibition of cytokine-dependent growth).
利用从健康供体获取的细胞，研究了分离的人CD4(+)或CD8(+) T细胞母细胞活化下调的机制。在缺乏白细胞介素-2（IL-2）的情况下，人CD4(+) T细胞母细胞对FasL和Apo2L/TRAIL均敏感，但人CD8(+) T细胞母细胞死亡，死亡受体连接无额外影响。CD8(+) T细胞母细胞比CD4(+) T细胞母细胞对IL-2剥夺诱导的凋亡更敏感，这与Bcl-2家族抗凋亡蛋白表达降低有关，尤其是CD8(+) T细胞母细胞中的Mcl-1。维持高水平的Bim表达也是必要的，因为在正常人CD8(+) T细胞母细胞中通过小干扰RNA（siRNA）下调Bim表达可大大降低IL-2剥夺诱导的凋亡。这些数据与之前的研究共同表明，免疫刺激细胞因子的存在与否在人CD8(+) T细胞反应调节类型（细胞因子剥夺导致的死亡与细胞因子依赖性生长的死亡受体抑制）中起重要作用。
