Overexpression of the Notch ligand, Jagged-1, induces alloantigen-specific human regulatory T cells
-
- Eric S. Yvon
- From the Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX.
-
- Stephane Vigouroux
- From the Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX.
-
- Raphael F. Rousseau
- From the Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX.
-
- Ettore Biagi
- From the Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX.
-
- Persis Amrolia
- From the Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX.
-
- Gianpietro Dotti
- From the Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX.
-
- Hans-Joachim Wagner
- From the Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX.
-
- Malcolm K. Brenner
- From the Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX.
Abstract
<jats:title>Abstract</jats:title><jats:p>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-γ, interleukin-2, and interleukin-5, but up-regulates transforming growth factor-β1 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. (Blood. 2003;102:3815-3821)</jats:p>
Journal
-
- Blood
-
Blood 102 (10), 3815-3821, 2003-11-15
American Society of Hematology
- Tweet
Keywords
Details 詳細情報について
-
- CRID
- 1360292621184997248
-
- NII Article ID
- 30022496366
-
- ISSN
- 15280020
- 00064971
-
- Data Source
-
- Crossref
- CiNii Articles