Mobilized Multipotent Hematopoietic Progenitors Promote Expansion and Survival of Allogeneic Tregs and Protect Against Graft Versus Host Disease.
Front Immunol
; 11: 607180, 2020.
Article
en En
| MEDLINE
| ID: mdl-33643294
ABSTRACT
Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) is routinely performed with peripheral blood stem cells (PBSCs) mobilized by injection of G-CSF, a growth factor which not only modulates normal hematopoiesis but also induces diverse immature regulatory cells. Based on our previous evidence that G-CSF-mobilized multipotent hematopoietic progenitors (MPP) can increase survival and proliferation of natural regulatory T cells (Tregs) in autoimmune disorders, we addressed the question how these cells come into play in mice and humans in an alloimmune setting. Using a C57BL/6 mouse model, we demonstrate that mobilized MPP enhance the immunosuppressant effect exerted by Tregs, against alloreactive T lymphocytes, both in vitro and in vivo. They do so by migrating to sites of allopriming, interacting with donor Tregs and increasing their numbers, thus reducing the lethality of graft-versus-host disease (GVHD). Protection correlates likewise with increased allospecific Treg counts. Furthermore, we provide evidence for a phenotypically similar MPP population in humans, where it shares the capacity to promote selective Treg expansion in vitro. We postulate that G-CSF-mobilized MPPs might become a valuable cellular therapy to expand donor Tregs in vivo and prevent GVHD, thereby making allo-HSCT safer for the treatment of leukemia patients.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Activación de Linfocitos
/
Linfocitos T Reguladores
/
Trasplante de Células Madre Hematopoyéticas
/
Traslado Adoptivo
/
Movilización de Célula Madre Hematopoyética
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Células Madre Multipotentes
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Proliferación Celular
/
Enfermedad Injerto contra Huésped
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Front Immunol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Francia