期刊
FRONTIERS IN IMMUNOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.607180
关键词
allogeneic HSCT; graft versus host disease; mobilization; multipotent progenitors; regulatory T cells; expansion; alloreactivity; mixed lymphocyte reaction
类别
资金
- APHP (Assistance Publique des Hopitaux de Paris)
- Institut National du Cancer
- Fondation ARC pour la Recherche contre le Cancer
- The Secular Society (TSS)
- TSS
Allo-HSCT often uses G-CSF to mobilize PBSCs, which can enhance the immunosuppressant effect of Tregs on alloreactive T cells, reducing the lethality of GVHD in mice and potentially in humans. This suggests G-CSF-mobilized MPPs could be a valuable cellular therapy to expand donor Tregs and prevent GVHD in allo-HSCT for leukemia treatment.
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.
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