Savary C A, Grazziuti M L, Przepiorka D, Tomasovic S P, McIntyre B W, Woodside D G, Pellis N R, Pierson D L, Rex J H
Department of Surgical Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.
In Vitro Cell Dev Biol Anim. 2001 Apr;37(4):216-22. doi: 10.1007/BF02577532.
Generation of an effective immune response requires that antigens be processed and presented to T lymphocytes by antigen-presenting cells, the most efficient of which are dendritic cells (DC). Because of their influence on both the innate and the acquired arms of immunity, a defect in DC would be expected to result in a broad impairment of immune function, not unlike that observed in astronauts during or after space flight. In the study reported here, we investigated whether DC generation and function are altered in a culture environment that models microgravity, i.e., the rotary-cell culture system (RCCS). We observed that RCCS supported the generation of DC identified by morphology, phenotype (HLA-DR+ and lacking lineage-associated markers), and function (high allostimulatory activity). However, the yield of DC from RCCS was significantly lower than that from static cultures. RCCS-generated DC were less able to phagocytose Aspergillus fumigatus conidia and expressed a lower density of surface HLA-DR. The proportion of DC expressing CD80 was also significantly reduced in RCCS compared to static cultures. When exposed to fungal antigens, RCCS-generated DC produced lower levels of interleukin-12 and failed to upregulate some costimulatory/adhesion molecules involved in antigen presentation. These data suggest that DC generation, and some functions needed to mount an effective immune response to pathogens, may be disturbed in the microgravity environment of space.
产生有效的免疫反应需要抗原呈递细胞将抗原加工并呈递给T淋巴细胞，其中最有效的抗原呈递细胞是树突状细胞（DC）。由于它们对先天性免疫和获得性免疫均有影响，因此预计DC的缺陷会导致免疫功能广泛受损，这与在太空飞行期间或之后宇航员身上观察到的情况并无不同。在本文报道的研究中，我们调查了在模拟微重力的培养环境即旋转细胞培养系统（RCCS）中，DC的生成和功能是否会发生改变。我们观察到，RCCS支持通过形态学、表型（HLA-DR+且缺乏谱系相关标志物）和功能（高同种异体刺激活性）鉴定的DC的生成。然而，RCCS中DC的产量明显低于静态培养中的产量。RCCS生成的DC吞噬烟曲霉菌分生孢子的能力较弱，且表面HLA-DR的表达密度较低。与静态培养相比，RCCS中表达CD80的DC比例也显著降低。当暴露于真菌抗原时，RCCS生成的DC产生的白细胞介素-12水平较低，并且未能上调一些参与抗原呈递的共刺激/黏附分子。这些数据表明，在太空的微重力环境中，DC的生成以及对病原体产生有效免疫反应所需的一些功能可能会受到干扰。
