CD70-CD27 ligation between neural stem cells and CD4+ T cells induces Fas-FasL-mediated T-cell death

Abstract

Introduction: Neural stem cells (NSCs) are among the most promising candidates for cell replacement therapy in neuronal injury and neurodegenerative diseases. One of the remaining obstacles for NSC therapy is to overcome the alloimmune response on NSCs by the host. Methods: To investigate the mechanisms of immune modulatory function derived from the interaction of human NSCs with allogeneic T cells, we examined the immune regulatory effects of human NSCs on allogeneic T cells in vitro. Results: Significantly, NSCs induced apoptosis of allogeneic T cells, in particular CD4(+) T cells. Interaction of CD70 on NSCs and CD27 on CD4(+) T cells mediated apoptosis of T cells. Thus, blocking CD70-CD27 interaction prevented NSC-mediated death of CD4(+) T cells. Conclusions: We present a rational explanation of NSC-induced immune escape in two consecutive stages. First, CD70 constitutively expressed on NSCs engaged CD27 on CD4(+) T cells, which induced Fas ligand expression on CD4(+) T cells. Second, CD4(+) T-cell apoptosis was followed by Fas-Fas ligand interaction in the CD4(+) T cells.