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
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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