Immune suppression of human lymphoid tissues and cells in rotating suspension culture and onboard the International Space Station

  • Wendy Fitzgerald
  • Silvia Chen
  • Carl Walz
  • Joshua Zimmerberg
  • Leonid Margolis
  • Jean-Charles GrivelEmail author


The immune responses of human lymphoid tissue explants or cells isolated from this tissue were studied quantitatively under normal gravity and microgravity. Microgravity was either modeled by solid body suspension in a rotating, oxygenated culture vessel or was actually achieved on the International Space Station (ISS). Our experiments demonstrate that tissues or cells challenged by recall antigen or by polyclonal activator in modeled microgravity lose all their ability to produce antibodies and cytokines and to increase their metabolic activity. In contrast, if the cells were challenged before being exposed to modeled microgravity suspension culture, they maintained their responses. Similarly, in microgravity in the ISS, lymphoid cells did not respond to antigenic or polyclonal challenge, whereas cells challenged prior to the space flight maintained their antibody and cytokine responses in space. Thus, immune activation of cells of lymphoid tissue is severely blunted both in modeled and true microgravity. This suggests that suspension culture via solid body rotation is sufficient to induce the changes in cellular physiology seen in true microgravity. This phenomenon may reflect immune dysfunction observed in astronauts during space flights. If so, the ex vivo system described above can be used to understand cellular and molecular mechanisms of this dysfunction.


Immune response Space flight Microgravity 



We thank the NASA ISS team of Expedition IV and the CBOSS team at Houston, especially Keith Holubec, Amy Klein, Todd Elliot, Jennifer Miller, Dianne Hammond, Eric Warren, Ron Lockett, Melanie Bilske, John Love, Tom Goodwin, Tacey Baker, Chris Gefrides, and Neal Pellis.


  1. Benner R.; van Oudenaren A.; de Ruiter H. Antibody formation in mouse bone marrow. IX. Peripheral lymphoid organs are involved in the initiation of bone marrow antibody formation. Cell. Immunol. 341: 125–137; 1977.CrossRefPubMedGoogle Scholar
  2. Cogoli A. Space flight and the immune system. Vaccine 115: 496–503; 1993.CrossRefPubMedGoogle Scholar
  3. Cogoli A.; Tschopp A. Lymphocyte reactivity during spaceflight. Immunol. Today 61: 1–4; 1985.CrossRefPubMedGoogle Scholar
  4. Cooper D.; Pellis N. R. Suppressed PHA activation of T lymphocytes in simulated microgravity is restored by direct activation of protein kinase C. J. Leukoc. Biol. 635: 550–562; 1998.PubMedGoogle Scholar
  5. Fitzgerald W.; Sylwester A. W.; Grivel J. C.; Lifson J. D.; Margolis L. B. Noninfectious X4 but not R5 human immunodeficiency virus type 1 virions inhibit humoral immune responses in human lymphoid tissue ex vivo. J. Virol. 7813: 7061–7068; 2004.CrossRefPubMedGoogle Scholar
  6. Glushakova S.; Baibakov B.; Margolis L. B.; Zimmerberg J. Infection of human tonsil histocultures: a model for HIV pathogenesis. Nat. Med. 112: 1320–1322; 1995.CrossRefPubMedGoogle Scholar
  7. Glushakova S.; Grivel J. C.; Fitzgerald W.; Sylwester A.; Zimmerberg J.; Margolis L. B. Evidence for the HIV-1 phenotype switch as a causal factor in acquired immunodeficiency. Nat. Med. 43: 346–349; 1998.CrossRefPubMedGoogle Scholar
  8. Goodwin T. J.; Prewett T. L.; Wolf D. A.; Spaulding G. F. Reduced shear stress: a major component in the ability of mammalian tissues to form three-dimensional assemblies in simulated microgravity. J. Cell. Biochem. 513: 301–311; 1993.CrossRefPubMedGoogle Scholar
  9. Hughes-Fulford M.; Lewis M. L. Effects of microgravity on osteoblast growth activation. Exp. Cell. Res. 2241: 103–109; 1996.CrossRefPubMedGoogle Scholar
  10. Ingber D. E. Tensegrity: the architectural basis of cellular mechanotransduction. Annu. Rev. Physiol. 59: 575–599; 1997.CrossRefPubMedGoogle Scholar
  11. Karlsson I.; Grivel J. C.; Chen S. S.; Karlsson A.; Albert J.; Fenyo E. M.; Margolis L. B. Differential pathogenesis of primary CCR5-using human immunodeficiency virus type 1 isolates in ex vivo human lymphoid tissue. J. Virol. 7917: 11151–11160; 2005.CrossRefPubMedGoogle Scholar
  12. Konstantinova I.; Rykova M.; Lesnyak A.; Antropova E. Immune changes during long-duration missions. J. Leukoc. Biol. 543: 189–201; 1993.PubMedGoogle Scholar
  13. Margolis L. B.; Fitzgerald W.; Glushakova S.; Hatfill S.; Amichay N.; Baibakov B.; Zimmerberg J. Lymphocyte trafficking and HIV infection of human lymphoid tissue in a rotating wall vessel bioreactor. AIDS Res. Hum. Retroviruses 1316: 1411–1420; 1997.CrossRefPubMedGoogle Scholar
  14. Montgomery P. O. Jr.; Cook J. E.; Reynolds R. C.; Paul J. S.; Hayflick L.; Stock D.; Schulz W. W.; Kimsey S.; Thirolf R. G.; Rogers T.; Campbell D. The response of single human cells to zero gravity. In Vitro 142: 165–173; 1978.CrossRefPubMedGoogle Scholar
  15. Nicogossian A. E.; Pool S. L.; Uri J. J. Historical Perspectives. In: Nicogossian A. E.; Huntoon C. L.; Pool S. L. (eds) Space Physiology and Medicine. Lea & Febinger, Philadelphia, pp 3–49; 1993.Google Scholar
  16. Schmitt D. A.; Hatton J. P.; Emond C.; Chaput D.; Paris H.; Levade T.; Cazenave J. P.; Schaffar L. The distribution of protein kinase C in human leukocytes is altered in microgravity. FASEB J. 1014: 1627–1634; 1996.PubMedGoogle Scholar
  17. Schwarz R. P.; Goodwin T. J.; Wolf D. A. Cell culture for three-dimensional modeling in rotating-wall vessels: an application of simulated microgravity. J. Tissue Cult. Methods 142: 51–57; 1992.CrossRefPubMedGoogle Scholar
  18. Sonnenfeld G.; Mandel A. D.; Konstantinova I. V.; Taylor G. R.; Berry W. D.; Wellhausen S. R.; Lesnyak A. T.; Fuchs B. B. Effects of spaceflight on levels and activity of immune cells. Aviat. Space Environ. Med. 617: 648–653; 1990.PubMedGoogle Scholar
  19. Sundaresan A.; Risin D.; Pellis N. R. Loss of signal transduction and inhibition of lymphocyte locomotion in a ground-based model of microgravity. In Vitro Cell. Dev. Biol. Anim. 382: 118–122; 2002.CrossRefPubMedGoogle Scholar
  20. Taylor G. R.; Janney R. P. In vivo testing confirms a blunting of the human cell-mediated immune mechanism during space flight. J. Leukoc. Biol. 512: 129–132; 1992.PubMedGoogle Scholar
  21. Taylor G. R.; Neale L. S.; Dardano J. R. Immunological analyses of U.S. Space Shuttle crewmembers. Aviat. Space Environ. Med. 573: 213–217; 1986.PubMedGoogle Scholar
  22. Tsao Y. D.; Goodwin T. J.; Wolf D. A.; Spaulding G. F. Responses of gravity level variations on the NASA/JSC bioreactor system. Physiologist 351 Suppl: S49–S50; 1992.PubMedGoogle Scholar
  23. Unsworth B. R.; Lelkes P. I. Growing tissues in microgravity. Nat. Med. 48: 901–907; 1998.CrossRefPubMedGoogle Scholar

Copyright information

© The Society for In Vitro Biology 2009

Authors and Affiliations

  • Wendy Fitzgerald
    • 1
  • Silvia Chen
    • 1
  • Carl Walz
    • 2
  • Joshua Zimmerberg
    • 1
  • Leonid Margolis
    • 1
  • Jean-Charles Grivel
    • 1
    Email author
  1. 1.NASA/NIH Center for Three-Dimensional Tissue Culture, Laboratory of Cellular and Molecular Biophysics, Program in Physical BiologyNational Institute of Child Health and Human Development, National Institutes of HealthBethesdaUSA
  2. 2.Astronaut OfficeNational Aeronautics and Space Administration, Johnson Space CenterHoustonUSA

Personalised recommendations