Splenic atrophy in experimental stroke is accompanied by increased regulatory T cells and circulating macrophages
Splenic atrophy in experimental stroke is accompanied by increased regulatory T cells and circulating macrophages
复制标题
DOI：
10.4049/jimmunol.176.11.6523
复制
发表时间：
2006-06-01
影响因子：
4.4
通讯作者：
Hurn, Patricia D.
中科院分区：
文献类型：
--
作者：
Offner, Halina;Subramanian, Sandhya;Hurn, Patricia D.
脑卒中的诱发不仅造成局部缺血和脑损伤，而且对外周免疫反应产生深远影响。在本研究中，我们评估了中风诱导后4天对脾和血细胞的影响。令人惊讶的是，与早期时间点相比，96小时大脑中动脉闭塞影响的右脑半球中的炎性细胞因子谱较少。此外，我们的研究结果表明，中风导致脾萎缩的特征在于器官大小的减少，脾细胞数量的急剧减少，以及在脾内处于凋亡晚期的膜联蛋白V+和TUNEL+细胞的诱导。这一过程的结果是减少T细胞增殖反应和炎性细胞因子的分泌，导致严重的免疫抑制状态。这些变化导致脾脏和血液中B细胞数量急剧减少，CD 4（+）FoxP 3（+）调节性T细胞数量增加。此外，我们检测到血液中非凋亡CD 11b（+）VLA-4阴性巨噬细胞/单核细胞的百分比显著增加。脑损伤后的免疫抑制可能是脑卒中后炎症因子减少的原因，但也可能会减少外周的保护性免疫反应。这些发现提供了新的证据来支持这样的论点，即脑缺血引起的脑损伤向外周免疫系统提供了强大的负信号，最终诱导由细胞死亡以及CD 4（+）FoxP 3（+）调节性T细胞的存在增加引起的剧烈的免疫抑制状态。
Induction of stroke not only produces local ischemia and brain damage, but also has profound effects on peripheral immune responses. In the current study, we evaluated effects on spleen and blood cells 4 days after stroke induction. Surprisingly, there was a less inflammatory cytokine profile in the middle cerebral artery occlusion-affected right brain hemisphere at 96 h compared with earlier time points. Moreover, our results demonstrate that stroke leads to splenic atrophy characterized by a reduction in organ size, a drastic loss of splenocyte numbers, and induction of annexin V+ and TUNEL+ cells within the spleen that are in the late stages of apoptosis. The consequence of this process was to reduce T cell proliferation responses and secretion of inflammatory cytokines, resulting in a state of profound immunosuppression. These changes produced a drastic reduction in B cell numbers in spleen and blood, and a novel increase in CD4(+)FoxP3(+) regulatory T cells. Moreover, we detected a striking increase in the percentage of nonapoptotic CD11b(+) VLA-4-negative macrophages/monocytes in blood. Immunosuppression in response to brain injury may account for the reduction of inflammatory factors in the stroke-affected brain, but also potentially could curtail protective immune responses in the periphery. These findings provide new evidence to support the contention that damage to the brain caused by cerebral ischemia provides a powerful negative signal to the peripheral immune system that ultimately induces a drastic state of immunosuppression caused by cell death as well as an increased presence of CD4(+)FoxP3(+) regulatory T cells.