Microgravity Science and Technology

, Volume 25, Issue 6, pp 343–352 | Cite as

The Lymphocyte Story – an Overview of Selected Highlights on the in Vitro Activation of Human Lymphocytes in Space

Original Article

Abstract

Since the first flight of humans into space it is known that space flight affects the immune system; especially a weakening of the reactivity of T-lymphocytes after flight has been observed. In an in vitro experiment, proposed by Augusto Cogoli and flown in Spacelab-1 in 1983, the activation of T-lymphocytes was found to be strongly inhibited in microgravity. This surprising result triggered extended investigations in space and on the ground by us and other research teams. T-cells are that subpopulation of lymphocytes responsible for the activation of the specific immune system. The mechanism of T-cell activation is very complex; 3 different signals are required as well as an interaction between T-lymphocytes and monocytes. Cell motility based on a continuous rearrangement of the cytoskeletal network within the cell is essential for cell-cell contacts. The objective of all our experiments performed on different platforms in space as well as in simulated microgravity on ground was to understand and explain the dysfunction of the cell activation under reduced gravity conditions. On sounding rockets we have studied the influence of microgravity on the delivery of the first signal, the motility of lymphocytes as well as changes in the cytoskeletal structure and early gene expression. On long term missions we investigated many aspects of the delivery of the 2 nd and 3 rd signal, including motility and aggregate formation of lymphocytes, interaction of lymphocytes with monocytes, motility of monocytes and changes in different cytoskeletal structures.

Keywords

Microgravity T-lymphocytes Monocytes Immune system 

References

  1. Albrecht-Buehler, G., Lancaster, R.M.: A quantitative description of the extension and retraction of surface protrusions in spreading 3T3 mouse fibroblasts. J. Cell Biol. 71, 370–382 (1976)CrossRefGoogle Scholar
  2. Bachmann, M.F., Oxenius, A.: Interleukin 2: from immunostimulation to immunoregulation and back again. EMBO Reports 8, 1142–1148 (2007)CrossRefGoogle Scholar
  3. Bechler, B., Cogoli, A., Mesland, D.: Lymphocyten sind schwerkraftempfindlich. Naturwissenschaften 73, 400–403 (1986)CrossRefGoogle Scholar
  4. Bechler, B., Cogoli, A., Cogoli - Greuter, M., Müller, O., Hunzinger, F., Criswell, S.B.: Activation of microcarrier-attached lymphocytes in microgravity. Biotechnol. Bioeng. 40, 991–996 (1992)CrossRefGoogle Scholar
  5. Brown, M.J., Hallam, J.A., Colucci-Guyon, E., Shaw, S.: Rigidity of circulating lymphocytes is primarily conferred by vimentin intermediate filaments. J. Immunol. 166, 6640–6646 (2001)CrossRefGoogle Scholar
  6. Buravkova, L.B., Romanov, Y.A.: The role of cytoskeleton in cell changes under condition of simulated microgravity. Acta Astronaut. 48, 647–650 (2001)CrossRefGoogle Scholar
  7. Carlsson, S.I.M., Bertilaccio, T.S., Ballabio, E., Maier, J.A.M.: Endothelial stress by gravity unloading: effects on cell growth and cytoskeletal organization. Biochim. Biophys. Acta 1642, 173–179 (2003)CrossRefGoogle Scholar
  8. Cogoli, A.: Changes observed in lymphocyte behavior during gravitational unloading. ASGSB Bull. (now Gravitat. Space Biol. Bull.) 4, 107–115 (1991)Google Scholar
  9. Cogoli, A.: The effect of hypogravity and hypergravity on cells of the immune system. J. Leukoc. Biol. 54, 259–268 (1993)Google Scholar
  10. Cogoli, A.: Gravitational physiology of human immune cells: a review of in vivo, ex vivo and in vitro studies. J. Grav. Physiol 3, 1–9 (1996)Google Scholar
  11. Cogoli, A.: Signal transduction in T-lymphocytes in microgravity. Grav. Space Biol. Bull. 10, 5–16 (1997)Google Scholar
  12. Cogoli, A.: Cell biology. In: Clement, G., Slenzka, K. (eds.) Fun- damental of Space Biology, pp. 121–170. Springer, Heidelberg (2006)Google Scholar
  13. Cogoli, A., Cogoli-Greuter, M.: Activation and proliferation of lymphocytes and other mammalian cells in microgravity. Adv. Space Biol. Med. 6, 33–79 (1997)CrossRefGoogle Scholar
  14. Cogoli, A., Cogoli-Greuter, M.: Cells of the immune system in space (lymphocytes). In: Brinckmann, E. (ed.) Biology in Space and Life on Earth, pp. 193–222. Wiley-VCH, Weinheim (2007)Google Scholar
  15. Cogoli, A., Bechler, B., Cogoli-Greuter, M., Criswell, S.B., Joller, H., Joller, P., Hunzinger, E., Müller, O.: Mitogenic signal transduction in T-lymphocytes in microgravity. J. Leukoc. Biol. 53, 569–575 (1993)Google Scholar
  16. Cogoli, A., Tschopp, A., Fuchs-Bislin, P.: Cell sensitivity to gravity. Science 225, 228–230 (1984)CrossRefGoogle Scholar
  17. Cogoli, M., Bechler, B., Cogoli, A., Arena, N., Barni, S., Pippia, P., Sechi, G., Valora, N., Monti, R.: Lymphocytes on sounding rockets. In: David, V. (ed.): Proceedings of the 4th European Sym- posium on Life Sciences Research in Space, Trieste, ESA SP - 307. pp. 229–234 ESA Publications Division, ESTEC, Noordwijk (1990)Google Scholar
  18. Cogoli-Greuter, M.: Effect of gravity changes on the cytoskeleton in human lymphocytes. Grav. Space. Bio. Bull. 17, 27–37 (2004)Google Scholar
  19. Cogoli-Greuter, M., Meloni, M.A., Sciola, L., Spano, A., Pippia, P., Monaco, G., Cogoli, A.: Movements and interactions of leukocytes in microgravity. J. Biotechnol. 47, 279–287 (1996)CrossRefGoogle Scholar
  20. Cogoli-Greuter, M., Spano, A., Sciola, L., Pippia, P., Cogoli, A.: Influence of microgravity on mitogen binding, motility and cytoskeleton patterns of T-lymphocytes and Jurkat cells– experiments on sounding rocket. Jap. J. Aerospace Env. Med. 35, 27–39 (1998)Google Scholar
  21. Friedrich, U.L.D., Joop, O., Pütz, Ch., Willich, G.: The slow rotating centrifuge microscope NIZEMI - a versatile instrument for terrestrial hypergravity and space microgravity research in biology and material science. J. Biotechnol. 47, 225–238 (1996)CrossRefGoogle Scholar
  22. Hashemi, B.B., Pensala, J.E., Vens, C., Huls, H., Cubbage, M.: Sams, C.F.:T cell activation response are differentially regulated during clinorotation and in spaceflight. FASEB J. 13, 2071–2082 (1999)Google Scholar
  23. Herranz, R., Anken, R., Boonstra, J., Braun, M., Christianen, P., Geest Martin de Hauslage, J., Hilbig, R., Hill, R., Lebert, M., Medina, J., Vagt, N., Ullrich, O., Loon, J., van Hemmersbach, R.: Ground-based facilities for simulation of microgravity, including terminology and organismic specific recommendations for their use. Astobiology 13, 1–17 (2013)CrossRefGoogle Scholar
  24. Horwitz, A.R., Parson, J.T.: Cell migration - movin’ on. Science 286, 1172–1174 (1999)CrossRefGoogle Scholar
  25. Hughes-Fulford, M., Lewis, M.L.: Effects of microgravity on osteoblasts growth activation. Exp. Cell Res. 224, 103–109 (1996)CrossRefGoogle Scholar
  26. Hughes-Fulford, M., Sugano, E., Schopper, T., Li, C.F., Boonyratanakornkit, J.B., Cogoli, A.: Early immune response and regulation of IL-2 receptor subunits. Cell Signal 17, 1111–1124 (2005)CrossRefGoogle Scholar
  27. Ingber, D.: How cells (might) sense microgravity. FASEB J. 13 Suppl., S3–S15 (1999)Google Scholar
  28. Janmey, P.A.: The cytoskeleton and cell signalling: component localization and mechanical coupling. Physiol. Rev. 78, 763–781 (1998)Google Scholar
  29. Kimzey, S.L.: Hematology and immunology on Skylab. In: Johnson, R.S., Dietlein. L.F. (eds.) Biomedical Results of Skylab, pp 249-282. NASA SP-377, Washington (1977)Google Scholar
  30. Kimzey, S.L., Fischer, C.L., Johnson, P.C., Ritzmann, S.E., Mengel, C.E.: Hematology and immunology studies. In: Biomedical Results of Apollo, pp 197-226. NASA SP-368, Washington (1975)Google Scholar
  31. Konstantinova, I.V., Antropova, Y.N., Legenkov, V.I., Zazhirey, V.D.: Study of reactivity of blood lymphoid cells in crew members of the Soyuz-6, Soyuz-7 and Soyuz-8 spaceships before and after flight. Space Biol. Med. 7, 48–55 (1973)Google Scholar
  32. Leonard, W.J., O’Shea, J.J.: Jaks and STATs: biological implications. Annu. Rev. Immunol. 16, 292–322 (1998)CrossRefGoogle Scholar
  33. Lewis, M.L.: The cytoskeleton, apoptosis, and gene expression in T-lymphocytes and other mammalian cells exposed to altered gravity. Adv. Space Biol. Med. 8, 77–128 (2002)CrossRefGoogle Scholar
  34. Lewis, M.L., Reynolds, J.L., Cubano, L.A., Hatton, J.P., Lawless, B.D., Piepmeier, E.H.: Spaceflight alters microtubules and increases apoptosis in human lymphocytes (Jurkat). FASEB J. 12, 1007–1018 (1998)Google Scholar
  35. Li, J., Zhang, S., Chen, J., Du, T., Wang, Y., Wang, Z.: Modeled microgravity causes changes in the cytoskeleton and focal adhesions, and decreases migration in malignant human MCF-7 cells. Protoplasma 238, 23–33 (2009)CrossRefGoogle Scholar
  36. Meloni, M.A., Galleri, G., Pippia, P., Cogoli-Greuter, M.: Cytoskeleton changes and impaired motility of monocytes in modeled low gravity. Protoplasma 229, 243–249 (2006)CrossRefGoogle Scholar
  37. Meloni, M.A., Galleri, G., Pani, G., Saba, A., Pippia, P., Cogoli-Greuter, M.: Space flight affects motility and cytoskeletal structures in human monocyte cell line J-111. Cytoskeleton 68, 125–137 (2011). doi:10.1002/cm.20499 CrossRefGoogle Scholar
  38. Pippia, P., Sciola, L., Cogoli-Greuter, M., Meloni, M.A., Spano, A., Cogoli, A.: Activation signals of T-lymphocytes in microgravity. J. Biotechnol. 47, 215–222 (1996)CrossRefGoogle Scholar
  39. Ratner, S., Jasti, R.K., Heppner, G.H.: Motility of murine lympocytes during transit through cell cycle. J. Immunol. 140, 583–588 (1988)Google Scholar
  40. Sanchez-Madrid, F., del Pozo, M.A.: Leukocyte polarization in cell migration and immune interactions. EMBO J. 18, 501–511 (1999)CrossRefGoogle Scholar
  41. Schatten, H., Lewis, M.L., Chakrabarti, A.: Spaceflight and clinorotation cause cytoskeleton and mitochondria changes and increases in apoptosis in cultured cells. Acta Astronaut. 49, 399–418 (2001)CrossRefGoogle Scholar
  42. Schwarzenberg, M., Pippia, P., Meloni, M.A., Cossu, G., Cogoli- Greuter, M., Cogoli, A.: Signal transduction in lymphocytes - a comparison of the data from space, the free fall machine and the random positioning machine. Adv. Space Res. 24, 793–800 (1999)CrossRefGoogle Scholar
  43. Smith-Garvin, J.E., Koretzky, G.A., Jordan, M.S.: T cell activation. Annu. Rev. Immunol. 27, 591–619 (2009)CrossRefGoogle Scholar
  44. Ullrich, O., Huber, K., Lang, K.: Signal transduction in cells of the immune system in microgravity. Cell Commun. Signal 6, 9 (2008)CrossRefGoogle Scholar
  45. Uva, B.M., Masini, M.A., Sturla, M., Prato, P., Passalacqua, M., Giuliani, M., Tagliafierro, G., Strollo, F.: Clinorotation-induced weightlessness influences the cytoskeleton of glial cells in culture. Brain Res. 934, 132–139 (2002)CrossRefGoogle Scholar
  46. Vadrucci, S., Henggeler, D., Lovis, P., Lambers, B., Cogoli, A.: Effects of vector-averaged gravity on the response to different stimulatory signals in T cells. J. Gravit. Physiol. 12, 177–178 (2005)Google Scholar
  47. Valitutti, S., Dessing, M., Aktories, K., Gallati, H., Lanzavecchia, A.: Sustained signaling leading to T cell activation results from prolonged T cell receptor occupancy. J. Exp. Med. 181, 577–584 (1995)CrossRefGoogle Scholar
  48. Vassy, J., Portet, S., Beil, M., Millot, G., Fauvel-Lafe‘ve, F, Karniguian, A., Gasset, G., Irinopoulou, T., Calvo, F., Rigaut, J.P., Schoevaert, D.: The effect of weightlessness on cytoskeleton architecture and proliferation of human breast cancer cell line MCF-7. FASEB J. 15, 1104–1106 (2001)Google Scholar
  49. Wilkison, P.C.: Leukocyte locomotion: Behavioural mechanisms for accumulation. J. Cell Sci. Suppl. 8, 104–119 (1987)Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Zero-g LifeTec GmbHZürichSwitzerland

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