Humoral and Cellular Immune Functions of Cytokine-Treated Schwann Cells

  • Gisela Wohlleben
  • Hans-Peter Hartung
  • Ralf Gold
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 468)


Until recently the peripheral nervous system (PNS) was thought to be one of the immune privileged sites, where no immune reaction can take place (Streilein, 1995). Thus this sensitive tissue could be protected from immune-mediated destruction. In the meantime it has become clear that cells of the immune system can cross the blood-nerve-barrier causing inflammation and damage of the nerve fibres and glial cells. When activated autoreactive T-cells enter the nervous system they can destroy the myelin sheath surrounding the axons, which is necessary for fast impulse conduction. Onset, progress, and consequences of the inflammatory demyelinating disease of the human peripheral nervous system, the Guillain-Barré-Syndrome (GBS), can be studied in its animal counterpart experimental autoimmune neuritis (EAN). EAN can be actively induced by immunization with the myelin proteins P2, PO, or peptides contained in them, or adoptively transferred by neuritogenic T-cells (AT-EAN).


Sciatic Nerve Schwann Cell Peripheral Nervous System Myelin Protein FasL Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Al-Ramadi B.K., Meissler Jr. J.J., Huang D., and Eisenstein T.K. (1992) Immunosuppression induced by nitric oxide and its inhibition by interleukin-4. Eur J Immunol, 22, 2249–2254.PubMedCrossRefGoogle Scholar
  2. Armati P.J., Pollard J.D., and Gatenby P. (1990) Rat and human Schwann cells in vitro can synthesize and express MHC molecules. Muscle Nerve, 13, 106–116.PubMedCrossRefGoogle Scholar
  3. Bergsteinsdottir K., Kingston A., Mirsky R., and Jessen K.R. (1991) Rat Schwann cells produce interleukin-1. J Neuroimmunol, 34, 15–23.PubMedCrossRefGoogle Scholar
  4. Bolin L.M., Verity N., Silver J.E., Shooter E.M., and Abrams J.S. (1995) Interleukin-6 production by Schwann cells and induction in sciatic nerve injury. J. Neurochem, 64, 850–858.PubMedCrossRefGoogle Scholar
  5. Bredt D.S. and Snyder S.H. (1992) Nitric oxide, a novel neuronal messenger. Neuron, 8, 3–11.PubMedCrossRefGoogle Scholar
  6. Chao D.T. and Korsmeyer S.J. (1998) BCL-2 FAMILY: Regulators of cell death. Annual Review of Immunology, 16, 395–419.PubMedCrossRefGoogle Scholar
  7. Constable A.L., Armati P.J., Toyka K.V., and Hartung H.R (1994) Production of prostanoids by Lewis rat Schwann cells in vitro. Brain Res, 635, 75–80.PubMedCrossRefGoogle Scholar
  8. Fu Y. and Blankenhorn E.P. (1992) Nitric oxide-induced anti-mitogenic effects in high and low responder rat strains. J Immunol, 148, 2217–2222.PubMedGoogle Scholar
  9. Gold R., Toyka K.V., and Hartung H.P. (1995) Synergistic effect of gamma-IFN and TNF-α on expression of immune molecules and antigen presentation by Schwann cells. Cell Immunol, 165, 65–70.PubMedCrossRefGoogle Scholar
  10. Gold R., Pepinsky R.B., Zettl U.K., Toyka K.V., and Hartung H.P. (1996a) Lipocortin-1 (annexin-1) suppresses activation of autoimmune T cell lines in the Lewis rat. Journal of Neuroimmunology, 69, 157–164.PubMedCrossRefGoogle Scholar
  11. Gold R., Zielasek J., Kiefer R., Toyka K.V., and Hartung H.P. (1996b) Secretion of nitrite by Schwann cells and its effect on T-cell activation in vitro. Cell Immunol, 168, 69–77.PubMedCrossRefGoogle Scholar
  12. Hartung H.P, Stoll G., and Toyka K.V. (1993) Immune reactions in the peripheral nervous system. In: Peripheral neuropathy. Edited by P.J. Dyck, P.K. Thomas, J.W. Griffin, P.A. Low, and J.F. Poduslo. Philadelphia: W.B. Saunders Company. 418–4Google Scholar
  13. Hua L.L., Liu J.S.H., Brosnan C.F., and Lee S.C. (1998) Selective inhibition of human glial inducible nitric oxide synthase by interferon-ß: Implications for multiple sclerosis. Annals of Neurology, 43, 384–387.PubMedCrossRefGoogle Scholar
  14. Husain N. (1998) Co-expression of Fas and Fas ligand in malignant glial tumors and cell lines. Acta Neuropathol, 95, 287–290. (Abstract)PubMedCrossRefGoogle Scholar
  15. Kingston A.E., Bergsteinsdottir K., Jessen K.R., Van Der Meide PH., Colston M.J., and Mirsky R. (1989) Schwann cells co-cultured with stimulated T cells and antigen express major histocompatibility complex (MHC) class II determinants without interferon-gamma pretreatment: synergistic effects of interferon-gamma and tumor necrosis factor on MHC class II induction. Eur J Immunol, 19, 177–183.PubMedCrossRefGoogle Scholar
  16. Kolb H. and Kolb-Bachofen V (1992) Nitric oxide: a pathogenetic factor in autoimmunity. Immunology Today, 13, 157–159.PubMedCrossRefGoogle Scholar
  17. Moncada S., Palmer R.M.J., and Higgs E.A. (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev, 43, 109–141.PubMedGoogle Scholar
  18. Morfin R., Young J., Corpechot C., Egestad B., Sjovall J., and Baulieu E.E. (1992) Neurosteroids: pregnenolone in human sciatic nerves. Proc Natl Acad Sci USA, 89, 6790–6793.PubMedCrossRefGoogle Scholar
  19. Nagata S. and Golstein P. (1995) The Fas death factor. Science, 267, 1449–1455.PubMedCrossRefGoogle Scholar
  20. Nussler A.K. and Biliar T.R. (1993) Inflammation, immunoregulation, and inducible nitric oxide synthase. J Leukocyte Biol, 54, 171–178.PubMedGoogle Scholar
  21. Streilein J.W. 1995 Unraveling immune privilige. Science 270 1158–1159Google Scholar
  22. Wekerle H., Schwab M., Linington C., and Meyermann R. (1986) Antigen presentation in the peripheral nervous system: Schwann cells present endogenous myelin autoantigens to lymphocytes. Eur J Immunol, 16, 1551–1557.PubMedCrossRefGoogle Scholar
  23. Yi Hu Z., Bourreau E., Jung-Testas I., Robel P., and Baulieu E.E. (1987) Neurosteroids: oligodendrocyte mitochondria convert cholesterol to pregnenolone. Proc Natl Acad Sci USA, 84, 8215–8219.CrossRefGoogle Scholar
  24. Zettl U.K., Mix E., Zielasek J., Stangel M., Hartung H.P, and Gold R. (1997) Apoptosis of myelin-reactive T cells induced by reactive oxygen and nitrogen intermediates in vitro. Cell Immunol, 178, 1–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Gisela Wohlleben
    • 2
  • Hans-Peter Hartung
    • 1
  • Ralf Gold
    • 2
  1. 1.Department of NeurologyUniversity of GrazAustria
  2. 2.Department of NeurologyUniversity of WürzburgWürzburgGermany

Personalised recommendations