title: Signal transduction in primary human T lymphocytes in altered gravity during parabolic flight and clinostat experiments.
abstract: OBJECTIVE
  Several limiting factors for human health and performance in microgravity have been clearly identified arising from the immune system, and substantial research activities are required in order to provide the basic information for appropriate integrated risk management. The gravity-sensitive nature of cells of the immune system renders them an ideal biological model in search for general gravity-sensitive mechanisms and to understand how the architecture and function of human cells is related to the gravitational force and therefore adapted to life on Earth.
  
  
  METHODS
  We investigated the influence of altered gravity in parabolic flight and 2D clinostat experiments on key proteins of activation and signaling in primary T lymphocytes. We quantified components of the signaling cascade 1.) in non-activated T lymphocytes to assess the "basal status" of the cascade and 2.) in the process of activation to assess the signal transduction.
  
  
  RESULTS
  We found a rapid decrease of CD3 and IL-2R surface expression and reduced p-LAT after 20 seconds of altered gravity in non-activated primary T lymphocytes during parabolic flight. Furthermore, we observed decreased CD3 surface expression, reduced ZAP-70 abundance and increased histone H3-acetylation in activated T lymphocytes after 5 minutes of clinorotation and a transient downregulation of CD3 and stable downregulation of IL-2R during 60 minutes of clinorotation.
  
  
  CONCLUSIONS
  CD3 and IL-2R are downregulated in primary T lymphocytes in altered gravity. We assume that a gravity condition around 1g is required for the expression of key surface receptors and appropriate regulation of signal molecules in T lymphocytes.
authors: Institute of Anatomy, Faculty of Medicine, University of Zurich, Zurich, Switzerland.
authors: Svantje
authors: S
authors: Tauber
authors: Swantje
authors: S
authors: Hauschild
authors: Katrin
authors: K
authors: Paulsen
authors: Annett
authors: A
authors: Gutewort
authors: Christiane
authors: C
authors: Raig
authors: Eva
authors: E
authors: Hürlimann
authors: Josefine
authors: J
authors: Biskup
authors: Claudia
authors: C
authors: Philpot
authors: Hartwin
authors: H
authors: Lier
authors: Frank
authors: F
authors: Engelmann
authors: Antonella
authors: A
authors: Pantaleo
authors: Augusto
authors: A
authors: Cogoli
authors: Proto
authors: P
authors: Pippia
authors: Liliana E
authors: LE
authors: Layer
authors: Cora S
authors: CS
authors: Thiel
authors: Oliver
authors: O
authors: Ullrich
mesh_terms: D017252:CD3 Complex / Q000096:biosynthesis*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D018470:Gravity, Altered; D006801:Humans; D007107:Immune System / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D012399:Rotation; D015398:Signal Transduction; D013026:Space Flight; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014893:Weightlessness; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis*
chemical_list: D017252:CD3 Complex; D015375:Receptors, Interleukin-2; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human