Efficient treatment of murine acute GvHD by in vitro expanded donor regulatory T cells

Autor: Petra Hoffmann, Christin Riegel, Kristina Doser, Tina J. Boeld, Matthias Edinger, Elisabeth Huber
Rok vydání: 2019
Předmět:
Cancer Research
Adoptive cell transfer
Bone marrow transplantation
Lymphocyte
Population
Graft vs Host Disease
chemical and pharmacologic phenomena
Bone Marrow Cells
T-Lymphocytes
Regulatory
Article
03 medical and health sciences
Mice
0302 clinical medicine
Immune system
immune system diseases
hemic and lymphatic diseases
Medicine
Animals
Transplantation
Homologous
Leukaemia
Myeloid Cells
IL-2 receptor
education
Cells
Cultured
030304 developmental biology
Inflammation
0303 health sciences
education.field_of_study
Mice
Inbred BALB C
business.industry
Allotransplantation
FOXP3
hemic and immune systems
Hematology
3. Good health
Transplantation
Mice
Inbred C57BL
Disease Models
Animal
medicine.anatomical_structure
surgical procedures
operative
Phenotype
Oncology
Immune System
Immunology
Peripheral tolerance
Female
Stem cell
business
030215 immunology
Zdroj: Leukemia
ISSN: 1476-5551
Popis: Acute graft-versus-host disease (aGvHD) is a frequent complication after allogeneic bone marrow/stem cell transplantation (BMT/SCT) induced by co-transplanted alloreactive conventional donor T cells. We previously demonstrated that the adoptive transfer of donor CD4+CD25+Foxp3+ regulatory T cells (Treg) at the time of BMT prevents aGvHD in murine models. Yet, the therapeutic potential of donor Treg for the treatment of established aGvHD has not yet been studied in detail. We now used in vitro expanded phenotypically and functionally stable murine Treg to explore their therapeutic efficacy in haploidentical aGvHD models. Upon transfer donor Treg ameliorate clinical and histologic signs of aGvHD and significantly improve survival. They migrate to lymphoid as well as aGvHD target organs, predominantly the gastrointestinal tract, where they inhibit the proliferation of conventional T cells, reduce the influx of myeloid cells, and the accumulation of inflammatory cytokines. Successfully treated animals restore aGvHD-induced tissue damage in target organs and lymphoid tissues, thereby supporting lymphocyte reconstitution. The therapeutically applied Treg population survives long term without conversion into pathogenic effector T cells. These results demonstrate that donor Treg not only prevent aGvHD, but are also efficacious for the treatment of this life-threatening BMT complication.
Databáze: OpenAIRE
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