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.

• Authors: Maud D'Aveni, Anne-Béatrice Notarantonio, Viviane A Agbogan, Allan Bertrand, Guillemette Fouquet, Pauline Gastineau, Meriem Garfa-Traoré, Marcelo De Carvalho, Olivier Hermine, Marie-Thérèse Rubio, Flora Zavala
• Journal: Frontiers in immunology (Front Immunol) Vol. 11 Pg. 607180 ( 2020) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 33643294 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 D’Aveni, Notarantonio, Agbogan, Bertrand, Fouquet, Gastineau, Garfa-Traoré, De Carvalho, Hermine, Rubio and Zavala.

Chemical References

• Cytokines

Topics

• Adoptive Transfer
• Animals
• Cell Proliferation
• Cells, Cultured
• Coculture Techniques
• Cytokines (metabolism)
• Disease Models, Animal
• Graft vs Host Disease (immunology, metabolism, prevention & control)
• Hematopoietic Stem Cell Mobilization
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Lymphocyte Activation
• Mice, Inbred BALB C
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mice, Transgenic
• Multipotent Stem Cells (immunology, metabolism)
• T-Lymphocytes, Regulatory (immunology, metabolism)