Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Microgravity Science and Technology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • 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)

    Article  Google Scholar 

  • Bachmann, M.F., Oxenius, A.: Interleukin 2: from immunostimulation to immunoregulation and back again. EMBO Reports 8, 1142–1148 (2007)

    Article  Google Scholar 

  • Bechler, B., Cogoli, A., Mesland, D.: Lymphocyten sind schwerkraftempfindlich. Naturwissenschaften 73, 400–403 (1986)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • Buravkova, L.B., Romanov, Y.A.: The role of cytoskeleton in cell changes under condition of simulated microgravity. Acta Astronaut. 48, 647–650 (2001)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • Cogoli, A.: Changes observed in lymphocyte behavior during gravitational unloading. ASGSB Bull. (now Gravitat. Space Biol. Bull.) 4, 107–115 (1991)

    Google Scholar 

  • Cogoli, A.: The effect of hypogravity and hypergravity on cells of the immune system. J. Leukoc. Biol. 54, 259–268 (1993)

    Google Scholar 

  • 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 

  • Cogoli, A.: Signal transduction in T-lymphocytes in microgravity. Grav. Space Biol. Bull. 10, 5–16 (1997)

    Google Scholar 

  • Cogoli, A.: Cell biology. In: Clement, G., Slenzka, K. (eds.) Fun- damental of Space Biology, pp. 121–170. Springer, Heidelberg (2006)

  • Cogoli, A., Cogoli-Greuter, M.: Activation and proliferation of lymphocytes and other mammalian cells in microgravity. Adv. Space Biol. Med. 6, 33–79 (1997)

    Article  Google Scholar 

  • 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)

  • 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 

  • Cogoli, A., Tschopp, A., Fuchs-Bislin, P.: Cell sensitivity to gravity. Science 225, 228–230 (1984)

    Article  Google Scholar 

  • 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)

  • Cogoli-Greuter, M.: Effect of gravity changes on the cytoskeleton in human lymphocytes. Grav. Space. Bio. Bull. 17, 27–37 (2004)

    Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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 

  • 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)

    Article  Google Scholar 

  • 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 

  • 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)

    Article  Google Scholar 

  • Horwitz, A.R., Parson, J.T.: Cell migration - movin’ on. Science 286, 1172–1174 (1999)

    Article  Google Scholar 

  • Hughes-Fulford, M., Lewis, M.L.: Effects of microgravity on osteoblasts growth activation. Exp. Cell Res. 224, 103–109 (1996)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • Ingber, D.: How cells (might) sense microgravity. FASEB J. 13 Suppl., S3–S15 (1999)

  • Janmey, P.A.: The cytoskeleton and cell signalling: component localization and mechanical coupling. Physiol. Rev. 78, 763–781 (1998)

    Google Scholar 

  • 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)

  • 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)

  • 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 

  • Leonard, W.J., O’Shea, J.J.: Jaks and STATs: biological implications. Annu. Rev. Immunol. 16, 292–322 (1998)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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 

  • Sanchez-Madrid, F., del Pozo, M.A.: Leukocyte polarization in cell migration and immune interactions. EMBO J. 18, 501–511 (1999)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • Smith-Garvin, J.E., Koretzky, G.A., Jordan, M.S.: T cell activation. Annu. Rev. Immunol. 27, 591–619 (2009)

    Article  Google Scholar 

  • Ullrich, O., Huber, K., Lang, K.: Signal transduction in cells of the immune system in microgravity. Cell Commun. Signal 6, 9 (2008)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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 

  • 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)

    Article  Google Scholar 

  • 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 

  • Wilkison, P.C.: Leukocyte locomotion: Behavioural mechanisms for accumulation. J. Cell Sci. Suppl. 8, 104–119 (1987)

    Google Scholar 

Download references

Acknowledgments

I would like to thank all teams which sustained us in this space adventure, especially our own team in Zürich and the team of the University of Sassari as well as the teams of ESA, NASA and RSC Energia as well as the teams of the sounding rocket flights involved in the integration of all our investigations. A special thank goes to all the astronauts and cosmonauts who performed our experiments with great skill and dedication.

Financial support was provided by the Swiss Federal Institute of Technology in Zürich, the European Space Agency and the PRODEX programme, the Italian Space Agency, the National Aeronautics and Space Administration, the Swiss National Science Foundation and Contraves Space.

Author information

Authors and Affiliations

  1. Zero-g LifeTec GmbH, Riedhofstrasse 273, 8049, Zürich, Switzerland

    Marianne Cogoli-Greuter

Authors
  1. Marianne Cogoli-Greuter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marianne Cogoli-Greuter.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cogoli-Greuter, M. The Lymphocyte Story – an Overview of Selected Highlights on the in Vitro Activation of Human Lymphocytes in Space. Microgravity Sci. Technol. 25, 343–352 (2014). https://doi.org/10.1007/s12217-014-9362-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12217-014-9362-4

Keywords

Search

Navigation