Third-party regulatory T cells prevent murine acute graft-versus-host disease
Open Access
- 1 September 2018
- journal article
- research article
- Published by Korean Association of Internal Medicine in The Korean Journal of Internal Medicine
- Vol. 33 (5), 980-989
- https://doi.org/10.3904/kjim.2016.319
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 x 10(5) T cell-depleted bone marrow cells and 5 x 10(5) CD4+CD25-splenic T cells from C57BL/6 (H-2b) mice. Recipients were injected with 5 x 10(5) cultured donor-, host-, or third-party-derived CD4+CD25+CD6 2L+ 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.Keywords
Funding Information
- Catholic University of Korea
- National Research Foundation of Korea (2016R1A2B4007282)
- Ministry of Health and Welfare
- Ministry of Education, Science and Technology
This publication has 22 references indexed in Scilit:
- Adoptive Transfer of Treg Cells Combined with Mesenchymal Stem Cells Facilitates Repopulation of Endogenous Treg Cells in a Murine Acute GVHD ModelPLOS ONE, 2015
- Combination Cell Therapy Using Mesenchymal Stem Cells and Regulatory T-Cells Provides a Synergistic Immunomodulatory Effect Associated with Reciprocal Regulation of Th1/Th2 and Th17/Treg Cells in a Murine Acute Graft-Versus-Host Disease ModelCell Transplantation, 2014
- Adoptive transfer of all-trans-retinal-induced regulatory T cells ameliorates experimental autoimmune arthritis in an interferon-gamma knockout modelAutoimmunity, 2012
- Combination of Intra-Bone Marrow–Bone Marrow Transplantation and Subcutaneous Donor Splenocyte Injection Diminishes Risk of Graft-Versus-Host Disease and Enhances Survival RateStem Cells and Development, 2011
- Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kineticsBlood, 2011
- [Influence of donor Treg cells on GVHD and GVL effects after allogeneic bone marrow transplantation in mice].2010
- Prevention of Graft-Versus-Host Disease by Intra-Bone Marrow Injection of Donor T CellsThe International Journal of Cell Cloning, 2007
- CD4+ CD25+ CD62+ T-Regulatory Cell Subset Has Optimal Suppressive and Proliferative PotentialAmerican Journal of Transplantation, 2004
- The role of donor T cells for target organ injuries in acute and chronic graft‐versus‐host diseaseImmunology, 2001
- A cell-surface molecule involved in organ-specific homing of lymphocytesNature, 1983