Donor Requirements for Regulatory T Cell Suppression of Murine Graft-versus-Host Disease
Autor: | Hidekazu Nishikii, Byung Su Kim, Maite Alvarez, Yuqiong Pan, Antonio Pierini, Dominik Schneidawind, Jeanette Baker, Lucrezia Colonna, Robert S. Negrin, Mareike Florek |
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Rok vydání: | 2015 |
Předmět: |
Homologous
Adoptive cell transfer Regulatory T cell T-Lymphocytes medicine.medical_treatment Immunology Gene Expression Graft vs Host Disease chemical and pharmacologic phenomena Hematopoietic stem cell transplantation CD8-Positive T-Lymphocytes Biology Inbred C57BL T-Lymphocytes Regulatory Article Mice medicine Animals Transplantation Homologous Immunology and Allergy IL-2 receptor Inbred BALB C Cell Proliferation Transplantation Mice Inbred BALB C Adoptive Transfer Biological Markers Forkhead Transcription Factors Histocompatibility Testing Interleukin-2 Receptor alpha Subunit Mice Inbred C57BL Tissue Donors Whole-Body Irradiation Hematopoietic Stem Cell Transplantation FOXP3 hemic and immune systems medicine.disease Regulatory surgical procedures operative Graft-versus-host disease medicine.anatomical_structure Biomarkers CD8 |
Zdroj: | The Journal of Immunology. 195:347-355 |
ISSN: | 1550-6606 0022-1767 |
Popis: | Adoptive transfer of freshly isolated natural occurring CD4+CD25+Foxp3+ regulatory T cells (Treg) prevents graft-versus-host disease (GVHD) in several animal models and following hematopoietic cell transplantation (HCT) in clinical trials. Donor-derived Treg have been mainly used, as they share the same MHC with CD4+ and CD8+ conventional T cells (Tcon) that are primarily responsible for GVHD. Third party–derived Treg are a promising alternative for cellular therapy, as they can be prepared in advance, screened for pathogens and activity, and banked. We explored MHC disparities between Treg and Tcon in HCT to evaluate the impact of different Treg populations in GVHD prevention and survival. Third-party Treg and donor Treg are equally suppressive in ex vivo assays, whereas both donor and third-party but not host Treg protect from GVHD in allogeneic HCT, with donor Treg being the most effective. In an MHC minor mismatched transplantation model (C57BL/6 → BALB/b), donor and third-party Treg were equally effective in controlling GVHD. Furthermore, using an in vivo Treg depletion mouse model, we found that Treg exert their main suppressive activity in the first 2 d after transplantation. Third-party Treg survive for a shorter period of time after adoptive transfer, but despite the shorter survival, they control Tcon proliferation in the early phases of HCT. These studies provide relevant insights on the mechanisms of Treg-mediated protection from GVHD and support for the use of third-party Treg in clinical trials. |
Databáze: | OpenAIRE |
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