Induction of immunological tolerance to myelinogenic glial-restricted progenitor allografts

Li, S; Oh, BC; Chu, CY; Arnold, A; Jablonska, A; Furtmuller, GJ; Qin, HM; Boltze, J; Magnus, T; Ludewig, P; Janowski, M; Brandacher, G; Walczak, P

Walczak, P (reprint author), Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, 733 N Broadway,647 MRB, Baltimore, MD 21205 USA.

BRAIN, 2019; 142 (): 3456

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.

Download PDF


Full Text Link