Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
Brain Behav Immun. 2017 Mar;61:274-288. doi: 10.1016/j.bbi.2016.12.027. Epub 2017 Jan 7.
Sleep generally regulates immune functions in a supportive manner and can affect parameters that are directly involved in the rejection process.
The first objective was to assess whether sleep deprivation (SD) or sleep restriction (SR) affects the allograft rejection process in mice. The second objective was to investigate whether the rejection process itself modulates the sleep pattern of allografted mice.
Adult BALB/c and C57BL/6J male mice were used as the donors and recipients, respectively, except for the syngeneic group (ISOTX), which received skin from mice of the same strain (C57BL/6J). The recipients were randomly assigned to either one of two control groups - TX (allogenic) or ISOTX (syngeneic) - which underwent stereotaxic surgery to enable sleep recording prior to the allograft but were not sleep deprived; one of two paradoxical sleep deprived groups - SDTX and TXSD - which underwent 72h of continuous SD either before or after the allograft respectively, and one of two sleep restricted groups - SRTX and TXSR - which underwent 21h of SD and 3h of sleep for 15days either before or after the allograft respectively.
The skin allograft was inspected daily to determine the survival time, expected as 8.0±0.4days in this transplant model under no treatment. The sleep pattern was controlled throughout the rejection process in the SD and SR groups. Draining lymph nodes, spleen, blood and skin grafts were harvested on the 5th day after transplantation for evaluation of the immune parameters related to allograft rejection.
In the control groups, we observed a reduction in paradoxical sleep throughout the entire allograft rejection process. Acute and chronic experimental sleep loss in the SD and SR groups produced marked alterations in the immune response. Both SD and SR prolonged allograft survival compared to the non-sleep-deprived group. There were reductions in the following parameters involved in the allograft rejection under sleep loss: CD4 and CD8 T cell subpopulations in the peripheral lymph organs and spleen, circulating sIL-2R levels, graft-infiltrating CD4 T cells and skin allograft global gene expression.
We provide, as far as we are aware, the first evidence in vivo that the immune response can alter the normal sleep pattern, and that sleep loss can conversely affect the immune response related to graft rejection.
睡眠通常以支持的方式调节免疫功能，并且可以影响直接参与排斥过程的参数。
第一个目的是评估睡眠剥夺（SD）或睡眠限制（SR）是否会影响小鼠的同种异体移植物排斥过程。第二个目的是研究排斥过程本身是否会调节同种异体移植小鼠的睡眠模式。
成年 BALB/c 和 C57BL/6J 雄性小鼠分别作为供体和受体，除同基因组（ISOTX）外，其接受来自同一品系（C57BL/6J）小鼠的皮肤。受体随机分配到两个对照组之一-TX（异体）或 ISOTX（同基因）-这些受体接受立体定向手术，以便在同种异体移植物前进行睡眠记录，但不受睡眠剥夺；两个异相睡眠剥夺组之一-SDTX 和 TXSD-分别在同种异体移植物前或后进行 72 小时的连续 SD，两个睡眠限制组之一-SRTX 和 TXSR-分别在同种异体移植物前或后进行 21 小时的 SD 和 3 小时的睡眠，持续 15 天。
每天检查皮肤移植物以确定存活时间，在无治疗情况下，该移植模型的预期存活时间为 8.0±0.4 天。在 SD 和 SR 组中，整个排斥过程的睡眠模式均受到控制。在移植后第 5 天收获引流淋巴结、脾脏、血液和皮肤移植物，以评估与同种异体移植物排斥相关的免疫参数。
在对照组中，我们观察到整个同种异体移植物排斥过程中异相睡眠减少。SD 和 SR 组中的急性和慢性实验性睡眠剥夺导致免疫反应明显改变。与非睡眠剥夺组相比，SD 和 SR 均延长了同种异体移植物的存活时间。在睡眠剥夺下，以下与同种异体移植物排斥相关的参数减少：外周淋巴器官和脾脏中的 CD4 和 CD8 T 细胞亚群、循环 sIL-2R 水平、移植物浸润的 CD4 T 细胞和皮肤移植物的整体基因表达。
我们提供了迄今为止体内的第一个证据，表明免疫反应可以改变正常的睡眠模式，而睡眠剥夺反过来又会影响与移植物排斥相关的免疫反应。
