Korean J Intern Med.  2018 Sep;33(5):980-989. 10.3904/kjim.2016.319.

Third-party regulatory T cells prevent murine acute graft-versus-host disease

Affiliations
  • 1Institute for Translational Research and Molecular Imaging, The Catholic University of Korea, Seoul, Korea. chosg@catholic.ac.kr
  • 2Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 3Department of Hematology, Catholic Blood and Marrow Transplantation Center, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea.

Abstract

BACKGROUND/AIMS
Adoptive therapy with regulatory T (Treg) cells to prevent graft-versus-host disease (GVHD) would benefit from a strategy to improve homing to the sites of inflammation following hematopoietic stem cell transplantation (HSCT). Although donor-derived Treg cells have mainly been used in these models, third-party-derived Treg cells are a promising alternative for cell-based immunotherapy, as they can be screened for pathogens and cell activity, and banked for GVHD prevention. In this study, we explored major histocompatibility complex (MHC) disparities between Treg cells and conventional T cells in HSCT to evaluate the impact of these different cell populations on the prevention of acute GVHD, as well as survival after allogeneic transplantation.
METHODS
To induce acute GVHD, lethally irradiated BALB/c (H-2d) mice were transplanted with 5 × 10⁵ T cell-depleted bone marrow cells and 5 × 10⁵ CD4+CD25- splenic T cells from C57BL/6 (H-2b) mice. Recipients were injected with 5 × 10⁵ cultured donor-, host-, or third-party-derived CD4+CD25+CD62L+ Treg cells (bone marrow transplantation + day 1).
RESULTS
Systemic infusion of three groups of Treg cell improved clinicopathological manifestations and survival in an acute GVHD model. Although donor-derived Treg cells were immunologically the most effective, the third-party-derived Treg cell therapy group displayed equal regulation of expansion of CD4+CD25+- Foxp3+ Treg cells and suppressive CD4+IL-17+ T-helper (Th17) cells in ex vivo assays compared with the donor- and host-derived groups.
CONCLUSIONS
Our findings demonstrate that the use of third-party Treg cells is a viable alternative to donor-derived Treg cellular therapy in clinical settings, in which human leukocyte antigen-matched donors are not always readily available.

Keyword

T-Lymphocytes, regulatory; Acute graft-versus host disease; Hematopoietic stem cell transplantation

MeSH Terms

Animals
Bone Marrow
Bone Marrow Cells
Graft vs Host Disease*
Hematopoietic Stem Cell Transplantation
Humans
Immunotherapy
Inflammation
Leukocytes
Major Histocompatibility Complex
Mice
T-Lymphocytes
T-Lymphocytes, Regulatory*
Tissue Donors
Transplantation, Homologous
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