Recipient-Derived Allo-iTregs Induced by Donor DCs Effectively Inhibit the Proliferation of Donor T Cells and Reduce GVHD

Autor: Pei-Jie Cao, Wen-Xin Liu, Jin-Shan Feng, Rui-Ting Wen, Zhi-Gang Yang, Hai-Tao Zhou
Rok vydání: 2018
Předmět:
0301 basic medicine
Histology
Primary Cell Culture
Graft vs Host Disease
chemical and pharmacologic phenomena
Spleen
Severity of Illness Index
T-Lymphocytes
Regulatory
03 medical and health sciences
Mice
0302 clinical medicine
Antigen
medicine
Potency
Animals
Humans
Transplantation
Homologous
IL-2 receptor
Ecology
Evolution
Behavior and Systematics
Bone Marrow Transplantation
Cell Proliferation
Mice
Inbred BALB C
Mice
Inbred C3H
Transplantation Chimera
business.industry
Immunomagnetic Separation
Graft Survival
FOXP3
hemic and immune systems
Dendritic Cells
Cell sorting
medicine.disease
Mixed lymphocyte reaction
Adoptive Transfer
Coculture Techniques
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Graft-versus-host disease
Immunology
Female
Anatomy
business
030217 neurology & neurosurgery
Biotechnology
Zdroj: Anatomical record (Hoboken, N.J. : 2007). 302(5)
ISSN: 1932-8494
Popis: To compare the potency of recipient-derived, antigen-specific regulatory T cells induced by different dendritic cells (DCs; iTregs) and freshly isolated natural regulatory T cells (nTregs) in preventing mouse graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). CD4+ T cells from recipient BALB/c mice were stimulated with DCs from recipient BALB/c (syn-DCs), donor B6 (allo-DCs), and third-party C3H (third-party-DCs) mice to induce different iTregs. In parallel, nTregs were isolated from spleen cells of recipient BALB/c (syn-nTregs) and donor B6 (allo-nTregs) mice using magnetic-activated cell sorting. Mixed lymphocyte reaction (MLR) assays were performed to evaluate the suppressive ability of these various regulatory T cells (Tregs). Both the iTregs and nTregs were transfused to GVHD mice on Days 0, 1, 3, and 5. Body weight, GVHD score, and survival time were monitored. Peripheral Tregs were subsequently examined on Days 7, 14, 21, and 28 after BMT, while chimerism was evaluated on Days 14 and 60. Histopathology of colon, liver, and spleen were also performed. DCs markedly induced CD25+ and Foxp3+ expression on CD4+ T cells. The allo-DC-induced Tregs (allo-iTregs) suppressed the proliferation of alloreactive T cells better than the other iTregs/nTregs in MLR assays (P < 0.05). Meanwhile, transfusion of the allo-iTregs reduced the severity of GVHD (P < 0.05), increased survival time compared with the GVHD group (P < 0.05), and enhanced the chimerism proportion. On Day 28 after BMT, the allo-iTregs group had the highest frequency of peripheral Tregs (P < 0.05). Recipient-derived allo-iTregs induced by donor DCs included predominant clones that specifically recognized donor antigens. These allo-iTregs not only prevented GVHD by suppressing the proliferation of donor-alloreactive T cells, but also promoted engraftment, and prolonged the survival of GVHD mice. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. Anat Rec, 302:825-836, 2019. © 2018 Wiley Periodicals, Inc.
Databáze: OpenAIRE
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