Graft-versus-host disease (GVHD) represents one of the major complications of allogeneic hematopoietic stem cell transplantation. Techniques to prevent GVHD have included ex vivo T-cell depletion of the graft or prolonged in vivo immunosuppression. Both reduce the frequency and severity of GVHD but also reduce T-cell-mediated graft-versus-malignancy effect, and increase the risk of infection. A major goal in transplantation is to prevent alloreactivity while preserving activity against tumors and infectious agents. We have used activation of the Notch pathway to try to generate T cells able to specifically regulate alloantigen responses. We used allogeneic Epstein-Barr virus lymphoblastoid B cells (EBV-LCLs) as stimulator cells. Such LCLs are excellent (allo) antigen-presenting cells and can be obtained in large numbers even from donors who have received extensive chemo/radiotherapy. We overexpressed a Notch ligand, Jagged-1, in these cells by adenoviral vector transduction. Stimulation of CD45RA+ naive T cells by Jagged-1 EBV-LCL reduces production of interferon-gamma, interleukin-2, and interleukin-5, but up-regulates transforming growth factor-beta 1 synthesis, consistent with induction of a regulatory T-cell phenotype. Transfer of these T cells to fresh lymphocyte cultures inhibits proliferative and cytotoxic immune responses to the priming alloantigens while sparing responses to third-party stimulator cells. Notch activation in the presence of alloantigen-presenting cells may therefore be a means of inducing specific regulatory T cells while preserving other T-cell functionality
Yvon, E., Vigouroux, S., Rousseau, R., Biagi, E., Amrolia, P., Dotti, G., et al. (2003). Overexpression of the Notch ligand, Jagged-1, induces alloantigen-specific human regulatory T cells. BLOOD, 102(10), 3815-3821 [10.1182/blood-2002-12-3826].
Citazione: | Yvon, E., Vigouroux, S., Rousseau, R., Biagi, E., Amrolia, P., Dotti, G., et al. (2003). Overexpression of the Notch ligand, Jagged-1, induces alloantigen-specific human regulatory T cells. BLOOD, 102(10), 3815-3821 [10.1182/blood-2002-12-3826]. | |
Tipo: | Articolo in rivista - Articolo scientifico | |
Carattere della pubblicazione: | Scientifica | |
Titolo: | Overexpression of the Notch ligand, Jagged-1, induces alloantigen-specific human regulatory T cells | |
Autori: | Yvon, E; Vigouroux, S; Rousseau, R; Biagi, E; Amrolia, P; Dotti, G; Wagner, H; Brenner, M | |
Autori: | ||
Data di pubblicazione: | 15-nov-2003 | |
Lingua: | English | |
Rivista: | BLOOD | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1182/blood-2002-12-3826 | |
Appare nelle tipologie: | 01 - Articolo su rivista |