Enhancement of Graft-Versus-Host Disease Control Efficacy by Adoptive Transfer of Type 1 Regulatory T Cells in Bone Marrow Transplant Model.
Stem Cells Dev
; 28(2): 129-140, 2019 01 15.
Article
en En
| MEDLINE
| ID: mdl-30381994
ABSTRACT
Interleukin (IL)-10-producing type 1 regulatory T (Tr1) cells, which are Foxp3-memory T lymphocytes, play important roles in peripheral immune tolerance. We investigated whether Tr1 cells exert immunoregulatory effects in a mouse model of acute graft-versus-host disease (GVHD). Mouse CD4+ T cells were induced to differentiate in vitro into Tr1 cells using vitamin D3 and dexamethasone, and these donor-derived Tr1 cells were infused on the day of bone marrow transplantation. The Tr1 cell-transferred group showed less weight-loss and a twofold higher survival rate than the GVHD group, together with markedly decreased histopathologic grades. It was associated with the expansion of CD4+IL-4+ type 2 T-helper (Th2) cells and CD4+CD25+Foxp3+ regulatory T (Treg) cells. Furthermore, Tr1 cells decreased the numbers of CD4+interferon-γ+ Th1 and CD4+IL-17+ Th17 cells. Recipient mice harbored some Foxp3+ Tregs due to adoptive transfer of Tr1 cells, together with the upregulated expression of costimulatory molecules, including cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and inducible T-cell costimulator (ICOS); however, the Treg cells did not show the plasticity. Therefore, adoptive Tr1 cell therapy may be effective against manifestations of GVHD, exert immunomodulatory effects in a manner dependent on CTLA-4 and ICOS, and induce differentiation of the transferred Tr1 cells into Foxp3+ Treg cells.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Trasplante de Médula Ósea
/
Linfocitos T Reguladores
/
Traslado Adoptivo
/
Enfermedad Injerto contra Huésped
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Stem Cells Dev
Asunto de la revista:
HEMATOLOGIA
Año:
2019
Tipo del documento:
Article