In Vitro Analyses of the Immunosuppressive Properties of Neural Stem/Progenitor Cells Using Anti-CD3/CD28-Activated T Cells

  • Virginie Bonnamain
  • Isabelle Neveu
  • Philippe Naveilhan
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 677)

Abstract

Neural stem/progenitor cells (NSPCs) are multi-potent cells defined by their ability to self-renew and differentiate into cells of glial and neuronal lineage. Because of these properties, NSPCs have been proposed as therapeutic tools to replace lost neurons. Recent observations in animal models of immune-related diseases indicate that NSPCs display immunomodulatory properties that might be a great interest for cell therapy. In particular, transplantation of NSPCs might be very useful as local immunosuppressive agent to promote the long-term survival of neuronal xenotransplant in the brain. To study this possibility, we have analysed the impact of NSPCs on anti-CD3/CD28-activated T cells. In vitro analyses clearly show that porcine, rat, and mouse NSPCs inhibit the proliferation of activated T cells. This result raises new perspectives concerning the use of NSPCs in cell therapy.

Key words

Neural progenitor Neural stem cell T cell Immunosuppression Culture Rat Pig Mouse 

References

  1. 1.
    Alvarez-Buylla, A., and Temple, S. (1998) Stem cells in the developing and adult nervous system. J. Neurobiol. 36, 105–110.PubMedCrossRefGoogle Scholar
  2. 2.
    Svendsen, C. N., and Smith, A. G. (1999) New prospects for human stem-cell therapy in the nervous system. Trends Neurosci. 22, 357–364.PubMedCrossRefGoogle Scholar
  3. 3.
    Martinez-Serrano, A., Rubio, F. J., Navarro, B., Bueno, C., and Villa, A. (2001) Human neural stem and progenitor cells: in vitro and in vivo properties, and potential for gene therapy and cell replacement in the CNS. Curr. Gene Ther. 1, 279–299.PubMedCrossRefGoogle Scholar
  4. 4.
    Bjorklund, A., and Lindvall, O. (2000) Cell replacement therapies for central nervous system disorders. Nat. Neurosci. 3, 537–544.PubMedCrossRefGoogle Scholar
  5. 5.
    Reynolds, B. A., Tetzlaff, W., and Weiss, S. (1992) A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J. Neurosci. 12, 4565–4574.PubMedGoogle Scholar
  6. 6.
    Reynolds, B. A., and Weiss, S. (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255, 1707–1710.PubMedCrossRefGoogle Scholar
  7. 7.
    Harrower, T. P., Tyers, P., Hooks, Y., and Barker, R. A. (2006) Long-term survival and integration of porcine expanded neural precursor cell grafts in a rat model of Parkinson’s disease. Exp. Neurol. 197, 56–69.PubMedCrossRefGoogle Scholar
  8. 8.
    Smith, P. M., and Blakemore, W. F. (2000) Porcine neural progenitors require commitment to the oligodendrocyte lineage prior to transplantation in order to achieve significant remyelination of demyelinated lesions in the adult CNS. Eur. J. Neurosci. 12, 2414–2424.PubMedCrossRefGoogle Scholar
  9. 9.
    Karbanova, J., Mokry, J., and Kotingova, L. (2004) Neural stem cells transplanted into intact brains as neurospheres form solid grafts composed of neurons, astrocytes and oligodendrocyte precursors. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. 148, 217–220.PubMedCrossRefGoogle Scholar
  10. 10.
    Einstein, O., Fainstein, N., Vaknin, I., Mizrachi-Kol, R., Reihartz, E., Grigoriadis, N., Lavon, I., Baniyash, M., Lassmann, H., and Ben-Hur, T. (2007) Neural precursors attenuate autoimmune encephalomyelitis by peripheral immunosuppression. Ann. Neurol. 61, 209–218.PubMedCrossRefGoogle Scholar
  11. 11.
    Einstein, O., Grigoriadis, N., Mizrachi-Kol, R., Reinhartz, E., Polyzoidou, E., Lavon, I., Milonas, I., Karussis, D., Abramsky, O., and Ben-Hur, T. (2006) Transplanted neural precursor cells reduce brain inflammation to attenuate chronic experimental autoimmune encephalomyelitis. Exp. Neurol. 198, 275–284.PubMedCrossRefGoogle Scholar
  12. 12.
    Pluchino, S., Quattrini, A., Brambilla, E., Gritti, A., Salani, G., Dina, G., Galli, R., Del Carro, U., Amadio, S., Bergami, A., Furlan, R., Comi, G., Vescovi, A. L., and Martino, G. (2003) Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature 422, 688–694.PubMedCrossRefGoogle Scholar
  13. 13.
    Pluchino, S., Zanotti, L., Rossi, B., Brambilla, E., Ottoboni, L., Salani, G., Martinello, M., Cattalini, A., Bergami, A., Furlan, R., Comi, G., Constantin, G., and Martino, G. (2005) Neurosphere-derived multipotent precursors promote neuroprotection by an immunomo dulatory mechanism. Nature 436, 266–271.PubMedCrossRefGoogle Scholar
  14. 14.
    Remy, S., Canova, C., Daguin-Nerriere, V., Martin, C., Melchior, B., Neveu, I., Charreau, B., Soulillou, J. P., and Brachet, P. (2001) Different mechanisms mediate the rejection of porcine neurons and endothelial cells transplanted into the rat brain. Xenotransplantation 8, 136–148.PubMedCrossRefGoogle Scholar
  15. 15.
    Michel, D. C., Nerriere-Daguin, V., Josien, R., Brachet, P., Naveilhan, P., and Neveu, I. (2006) Dendritic cell recruitment following xenografting of pig fetal mesencephalic cells into the rat brain. Exp. Neurol. 202, 76–84.PubMedCrossRefGoogle Scholar
  16. 16.
    Sergent-Tanguy, S., Veziers, J., Bonnamain, V., Boudin, H., Neveu, I., and Naveilhan, P. (2006) Cell surface antigens on rat neural progenitors and characterization of the CD3 (+)/CD3 (−) cell populations. Differentiation 74, 530–541.PubMedCrossRefGoogle Scholar
  17. 17.
    Dugast, A. S., Haudebourg, T., Coulon, F., Heslan, M., Haspot, F., Poirier, N., Vuillefroy de Silly, R., Usal, C., Smit, H., Martinet, B., Thebault, P., Renaudin, K., and Vanhove, B. (2008) Myeloid-derived suppressor cells accumulate in kidney allograft tolerance and specifically suppress effector T cell expansion. J. Immunol. 180, 7898–7906.PubMedGoogle Scholar

Copyright information

© Humana Press 2010

Authors and Affiliations

  • Virginie Bonnamain
    • 1
    • 2
    • 3
  • Isabelle Neveu
    • 1
    • 2
    • 3
  • Philippe Naveilhan
    • 1
    • 2
    • 3
  1. 1.INSERM UMR 643NantesFrance
  2. 2.Institut de Transplantation et de Recherche en Transplantation (ITERT)CHU NantesNantesFrance
  3. 3.Faculté de MédecineUniversité de NantesNantesFrance

Personalised recommendations