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Mobilized Multipotent Hematopoietic Progenitors Promote Expansion and Survival of Allogeneic Tregs and Protect Against Graft Versus Host Disease

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.
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https://hal-univ-paris.archives-ouvertes.fr/hal-03253594
Contributor : Flora Zavala <>
Submitted on : Tuesday, June 8, 2021 - 1:09:56 PM
Last modification on : Tuesday, July 13, 2021 - 3:15:06 AM
Long-term archiving on: : Thursday, September 9, 2021 - 7:08:42 PM

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Maud D’aveni, Anne-Béatrice Notarantonio, Viviane Agbogan, Allan Bertrand, Guillemette Fouquet, et al.. Mobilized Multipotent Hematopoietic Progenitors Promote Expansion and Survival of Allogeneic Tregs and Protect Against Graft Versus Host Disease. Frontiers in Immunology, Frontiers, 2021, 11, ⟨10.3389/fimmu.2020.607180⟩. ⟨hal-03253594⟩

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