Induction of immunological tolerance to myelinogenic glial-restricted progenitor allografts

Shen Li, Byoung Chol Oh, Chengyan Chu, Antje Arnold, Anna Jablonska, Georg J. Furtmüller, Hua Min Qin, Johannes Boltze, Tim Magnus, Peter Ludewig, Miroslaw Janowski, Gerald Brandacher, Piotr Walczak

Research output: Contribution to journalArticle

Abstract

The immunological barrier currently precludes the clinical utilization of allogeneic stem cells. Although glial-restricted progenitors have become attractive candidates to treat a wide variety of neurological diseases, their survival in immunocompetent recipients is limited. In this study, we adopted a short-term, systemically applicable co-stimulation blockade-based strategy using CTLA4-Ig and anti-CD154 antibodies to modulate T-cell activation in the context of allogeneic glial-restricted progenitor transplantation. We found that co-stimulation blockade successfully prevented rejection of allogeneic glial-restricted progenitors from immunocompetent mouse brains. The long-term engrafted glial-restricted progenitors myelinated dysmyelinated adult mouse brains within one month. Furthermore, we identified a set of plasma miRNAs whose levels specifically correlated to the dynamic changes of immunoreactivity and as such could serve as biomarkers for graft rejection or tolerance. We put forward a successful strategy to induce alloantigen-specific hyporesponsiveness towards stem cells in the CNS, which will foster effective therapeutic application of allogeneic stem cells.

Original languageEnglish (US)
Pages (from-to)3456-3472
Number of pages17
JournalBrain
Volume142
Issue number11
DOIs
StatePublished - Nov 1 2019

Keywords

  • Co-stimulation blockade
  • Glial-restricted progenitors
  • Immunological tolerance
  • Myelination
  • Transplantation

ASJC Scopus subject areas

  • Clinical Neurology

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  • Cite this

    Li, S., Oh, B. C., Chu, C., Arnold, A., Jablonska, A., Furtmüller, G. J., Qin, H. M., Boltze, J., Magnus, T., Ludewig, P., Janowski, M., Brandacher, G., & Walczak, P. (2019). Induction of immunological tolerance to myelinogenic glial-restricted progenitor allografts. Brain, 142(11), 3456-3472. https://doi.org/10.1093/brain/awz275