(Leukin-2) Role of Interleukin-2 Receptor in Signal Transduction and Gravisensing Threshold of T-Lymphocytes
T-LYMPHOCYTES (LEUKIN-2)
Research Area: Cellular Biology
Expedition(s): 14
Principal Investigator(s): ● Isabelle Walther, PhD, Swiss Federal Institute of Technology,
Space Biology, Zurich, Switzerland
● August Cogoli, PhD, Zero-g Tec GmbH, Zurich, Switzerland
● Proto Pippia, University of Sassari, Sassari, Italy
● Millie Hughes-Fulford, PhD, University of California, San
Francisco, California
RESEARCH OBJECTIVES
The Role of Interleukin-2 Receptor in Signal Transduction and Gravisensing Threshold of T-
Lymphocytes (Leukin-2) experiment studies the signal transduction pathway of the activation of
T-lymphocytes. This investigation determines if loss of the Interleukin-2 receptor (IL-2)
expression is the cause of inhibition. Microgravity is used as an inhibitor of activation.
EARTH BENEFITS
Determining the factors that cause IL-2 suppression can help scientists on Earth better treat
immunosuppressed patients.
SPACE BENEFITS
Leukin-2 may help scientists better understand the depression of the immune system, which
occurs during spaceflight and, therefore, to devise more adequate preventive or corrective
measures for crew members during long-duration missions.
RESULTS
Human T cells were stimulated with Con A and anti-CD28 aboard the International Space
Station (ISS) to induce immune responses. Microarray expression analysis after 1.5 hours of
activation demonstrated that the T cells activated in microgravity (during flight on the ISS) had
distinct patterns of global gene expression that differed from those activated in a 1-g centrifuge
during spaceflight (control or normal gravity that can be run during spaceflight). Forty-seven
genes were identified that were significantly differentially down-regulated in T cells exposed to
microgravity compared with T cells exposed to microgravity in a 1-g centrifuge. Activation of
Rel/NF-κB, CREB (a transcription factor that is known for its role in cell proliferation,
differentiation, and survival), and serum response factor gene targets, genes important in
immune cell function pathways, was down-regulated. These data suggest that the tumor
necrosis factor (TNF) pathway is a major early downstream effector pathway inhibited in
microgravity, and this could lead to ineffective, pro-inflammatory host defenses against
infections during long-term spaceflight. These results may suggest that there could be a direct
effect of microgravity on the expression of genes controlling immune cell function.