Signal transduction in cells of the immune system in microgravity

Early reports about disturbed immune cell function in space date back in the 70ties, where reduced reactivity of blood lymphoid cells has been discovered in crew members of Soyuz spaceships and of Skylab and Apollo [1,2]. Recently, a subclinical re-activation varicella zoster virus (VZV) has been reported in astronauts [3,4], a virus which becomes latent in the nervous system after primary infection, but is reactivated frequently in immune suppressed individuals, such as after organ transplantation, and in patients with cancer or AIDS. Whereas it is well known that gravity can be perceived by gravireceptors (statocyst-like organelles or gravisensitive ion channels in the cell membrane) in unicellular organisms such as Paramecium and Loxodes, where it strongly influences intracellular signal transduction and behaviour [5,6], the molecular mechanisms of gravisensitivity in mammalian cells are widely unknown. After the pioneering discovery of Cogoli et al. at the first Spacelab-Mission 20 years ago [7], it is known that proliferative response of lymphocytes after mitogenic stimulation is suppressed in microgravity [8]. In follow-up experiments in order to verify the result from Spacelab 1, it has been demonstrated clearly that factors other than microgravity can be excluded to be responsible for the depressed activation of lymphocytes. Whereas the phenomenon of reduced activation of T cells during microgravity is well described [9,10] and verified, the exact molecular mechanisms are not elucidated.Several investigations evidence alterations in signal transduction in lymphocytes. In lymphocytes, microgravity affected the protein kinase C [11,12] whereas delivery of first activation signal, patching and capping of conA-binding membrane proteins occurred normally in spaceflight [13]. These findings suggest the existence of gravisensitive cellular targets upstream from PKC and downstream from the TCR/CD3, where the lipid-raft-associated membrane-proximal signalosome comple