Gridley Daila S, Pecaut Michael J, Rizvi Asma, Coutrakon George B, Luo-Owen Xian, Makinde Adeola Y, Slater James M
Department of Radiation Medicine, Radiation Research Laboratories, Loma Linda University, CA 92354, USA.
Int J Radiat Biol. 2009 Mar;85(3):250-61. doi: 10.1080/09553000902748609.
To evaluate cluster of differentiation 4(+) (CD4(+)) T cell gene expression and related parameters after whole-body exposure to proton radiation as it occurs in the spaceflight environment.
C57BL/6 mice were irradiated to total doses of 0, 0.01, 0.05, and 0.1 gray (Gy) at 0.1 cGy/h. On day 0 spleens were harvested from a subset in the 0, 0.01 and 0.1 Gy groups; (CD4(+)) T cells were isolated; and expression of 84 genes relevant to T helper (Th) cell function was determined using reverse transcriptase-polymerase chain reaction (RT-PCR). Remaining mice were euthanized on days 0, 4, and 21 for additional analyses.
Genes with >2-fold difference and p < 0.05 compared to 0 Gy were noted. After 0.01 Gy, five genes were up-regulated (Ccr5, Cd40, Cebpb, Igsf6, Tnfsf4) and three were down-regulated (Il4ra, Mapk8, Nfkb1). After 0.1 Gy there were nine up-regulated genes (Ccr4, Cd40, Cebpb, Cxcr3, Socs5, Stat4, Tbx21, Tnfrsf4, Tnfsf4); none were down-regulated. On day 0 after 0.01 Gy, CD4(+) T cell counts and CD4:CD8 ratio were low in the spleen (p < 0.05). Spontaneous DNA synthesis in both spleen and blood was lowest in the 0.01 Gy group on day 0; on days 4 and 21 all p values were >0.1.
The data show that the pattern of gene expression in CD4(+) T cells after protracted low-dose proton irradiation was significantly modified and highly dependent upon total dose. The findings also suggest that low-dose radiation, especially 0.01 Gy, may enhance CD4(+) T cell responsiveness.
评估在太空飞行环境中全身暴露于质子辐射后，分化簇4（+）（CD4（+））T细胞的基因表达及相关参数。
以0.1厘戈瑞/小时的剂量率，将C57BL/6小鼠分别照射至总剂量为0、0.01、0.05和0.1戈瑞（Gy）。在第0天，从0、0.01和0.1 Gy组的部分小鼠中采集脾脏；分离出CD4（+）T细胞；使用逆转录聚合酶链反应（RT-PCR）测定与辅助性T（Th）细胞功能相关的84个基因的表达。其余小鼠在第0、4和21天实施安乐死以进行额外分析。
发现与0 Gy相比，差异倍数>2且p<0.05的基因。0.01 Gy照射后，有5个基因上调（Ccr5、Cd40、Cebpb、Igsf6、Tnfsf4），3个基因下调（Il4ra、Mapk8、Nfkb1）。0.1 Gy照射后有9个基因上调（Ccr4、Cd40、Cebpb、Cxcr3、Socs5、Stat4、Tbx21、Tnfrsf4、Tnfsf4）；无基因下调。0.01 Gy照射后第0天，脾脏中CD4（+）T细胞计数及CD4:CD8比值较低（p<0.05）。第0天，0.01 Gy组脾脏和血液中的自发DNA合成最低；第4天和第21天，所有p值均>0.1。
数据表明，长时间低剂量质子照射后CD4（+）T细胞中的基因表达模式发生了显著改变，且高度依赖于总剂量。研究结果还表明，低剂量辐射，尤其是0.01 Gy，可能增强CD4（+）T细胞的反应性。
