Hwang Shen-An, Crucian Brian, Sams Clarence, Actor Jeffrey K
Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, Texas, United States of America.
Division of Biomedical and Environmental Sciences, NASA Johnson Space Center, Houston, Texas, United States of America.
PLoS One. 2015 May 13;10(5):e0124380. doi: 10.1371/journal.pone.0124380. eCollection 2015.
Alterations in immune function have been documented during or post-spaceflight and in ground based models of microgravity. Identification of immune parameters that are dysregulated during spaceflight is an important step in mitigating crew health risks during deep space missions. The in vitro analysis of leukocyte activity post-spaceflight in both human and animal species is primarily focused on lymphocytic function. This report completes a broader spectrum analysis of mouse lymphocyte and monocyte changes post 13 days orbital flight (mission STS-135). Analysis includes an examination in surface markers for cell activation, and antigen presentation and co-stimulatory molecules. Cytokine production was measured after stimulation with T-cell mitogen or TLR-2, TLR-4, or TLR-5 agonists. Splenocyte surface marker analysis immediate post-spaceflight and after in vitro culture demonstrated unique changes in phenotypic populations between the flight mice and matched treatment ground controls. Post-spaceflight splenocytes (flight splenocytes) had lower expression intensity of CD4+CD25+ and CD8+CD25+ cells, lower percentage of CD11c+MHC II+ cells, and higher percentage of CD11c+MHC I+ populations compared to ground controls. The flight splenocytes demonstrated an increase in phagocytic activity. Stimulation with ConA led to decrease in CD4+ population but increased CD4+CD25+ cells compared to ground controls. Culturing with TLR agonists led to a decrease in CD11c+ population in splenocytes isolated from flight mice compared to ground controls. Consequently, flight splenocytes with or without TLR-agonist stimulation showed a decrease in CD11c+MHC I+, CD11c+MHC II+, and CD11c+CD86+ cells compared to ground controls. Production of IFN-γ was decreased and IL-2 was increased from ConA stimulated flight splenocytes. This study demonstrated that expression of surface molecules can be affected by conditions of spaceflight and impaired responsiveness persists under culture conditions in vitro.
在太空飞行期间、之后以及地面微重力模型中,均已记录到免疫功能的改变。识别太空飞行期间失调的免疫参数是降低深空任务中机组人员健康风险的重要一步。对人类和动物物种太空飞行后白细胞活性的体外分析主要集中在淋巴细胞功能上。本报告完成了对小鼠在13天轨道飞行(STS - 135任务)后淋巴细胞和单核细胞变化的更广泛分析。分析包括检查细胞活化的表面标志物、抗原呈递和共刺激分子。在用T细胞有丝分裂原或TLR - 2、TLR - 4或TLR - 5激动剂刺激后测量细胞因子的产生。太空飞行后立即以及体外培养后的脾细胞表面标志物分析表明,飞行小鼠与匹配的地面处理对照之间的表型群体存在独特变化。与地面对照相比,太空飞行后的脾细胞(飞行脾细胞)CD4 + CD25 +和CD8 + CD25 +细胞的表达强度较低,CD11c + MHC II +细胞的百分比较低,而CD11c + MHC I +群体的百分比更高。飞行脾细胞的吞噬活性增加。与地面对照相比,用ConA刺激导致CD4 +群体减少,但CD4 + CD25 +细胞增加。与地面对照相比,用TLR激动剂培养导致从飞行小鼠分离的脾细胞中CD11c +群体减少。因此,与地面对照相比,无论有无TLR激动剂刺激,飞行脾细胞中CD11c + MHC I +、CD11c + MHC II +和CD11c + CD86 +细胞均减少。ConA刺激的飞行脾细胞中IFN - γ的产生减少,IL - 2增加。本研究表明,表面分子的表达可受太空飞行条件影响,且在体外培养条件下反应性受损仍会持续存在。