Human iPSC-derived CD4+ Treg-like cells engineered with chimeric antigen receptors control GvHD in a xenograft model.
Cell Stem Cell
; 31(6): 795-802.e6, 2024 Jun 06.
Article
en En
| MEDLINE
| ID: mdl-38848686
ABSTRACT
CD4+ T cells induced from human iPSCs (iCD4+ T cells) offer a therapeutic opportunity for overcoming immune pathologies arising from hematopoietic stem cell transplantation. However, most iCD4+ T cells are conventional helper T cells, which secrete inflammatory cytokines. We induced high-level expression of FOXP3, a master transcription factor of regulatory T cells, in iCD4+ T cells. Human iPSC-derived, FOXP3-induced CD4+ T (iCD4+ Treg-like) cells did not secrete inflammatory cytokines upon activation. Moreover, they showed demethylation of the Treg-specific demethylation region, suggesting successful conversion to immunosuppressive iCD4+ Treg-like cells. We further assessed these iCD4+ Treg-like cells for CAR-mediated immunosuppressive ability. HLA-A2 CAR-transduced iCD4+ Treg-like cells inhibited CD8+ cytotoxic T cell (CTL) division in a mixed lymphocyte reaction assay with A2+ allogeneic CTLs and suppressed xenogeneic graft-versus-host disease (GVHD) in NSG mice treated with A2+ human PBMCs. In most cases, these cells suppressed the xenogeneic GvHD progression as much as natural CD25+CD127- Tregs did.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T Reguladores
/
Células Madre Pluripotentes Inducidas
/
Receptores Quiméricos de Antígenos
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Enfermedad Injerto contra Huésped
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Stem Cell
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos