Signal Transduction in Primary Human T\ud Lymphocytes in Altered Gravity During\ud Parabolic Flight and Clinostat Experiments

摘要

Background/Aims: Several limiting factors for human health and performance in microgravity\udhave been clearly identified arising from the immune system, and substantial research\udactivities are required in order to provide the basic information for appropriate integrated\udrisk management. The gravity-sensitive nature of cells of the immune system renders them an\udideal biological model in search for general gravity-sensitive mechanisms and to understand\udhow the architecture and function of human cells is related to the gravitational force and\udtherefore adapted to life on Earth. Methods: We investigated the influence of altered gravity\udin parabolic flight and 2D clinostat experiments on key proteins of activation and signaling\udin primary T lymphocytes. We quantified components of the signaling cascade 1.) in nonactivated\udT lymphocytes to assess the “basal status” of the cascade and 2.) in the process\udof activation to assess the signal transduction. Results: We found a rapid decrease of CD3\udand IL-2R surface expression and reduced p-LAT after 20 seconds of altered gravity in nonactivated\udprimary T lymphocytes during parabolic flight. Furthermore, we observed decreased\udCD3 surface expression, reduced ZAP-70 abundance and increased histone H3-acetylation in activated T lymphocytes after 5 minutes of clinorotation and a transient downregulation\udof CD3 and stable downregulation of IL-2R during 60 minutes of clinorotation. Conclusion:\udCD3 and IL-2R are downregulated in primary T lymphocytes in altered gravity. We assume\udthat a gravity condition around 1g is required for the expression of key surface receptors and\udappropriate regulation of signal molecules in T lymphocytes.