Abstract | BACKGROUND: Obliterative bronchiolitis (OB) ranks as the major obstacle for long-term survival of lung transplantation patients. Rapamycin (Rapa) has recently been confirmed as an immunosuppressant for antirejection due to its suppressive role in T cell activation. Here, we explore the effect of Rapa combined with immature dendritic cells (imDCs) on OB in trachea allograft rats. METHODS: The effect of bone marrow-derived imDCs or Rapa-imDCs on lymphocyte cells and CD4+ T cells were evaluated by methyl thiazolyl tetrazolium and flow cytometry. Tracheal transplantation was performed from Lewis rats to Wistar recipients. Recipient rats received Rapa+imDCs for 10 consecutive days after implantation. Allograft rejection was assessed by micro-CT image, hematoxylin/eosinHE staining and flow cytometry. The underlying mechanism was also investigated. RESULTS: Rapa-imDCs inhibited lymphocyte and CD4+ T cell growth. Furthermore, Rapa-imDC treatment induced T cell hyporesponsiveness by attenuating T cell differentiation into IFN-x03B3;-producing T cells (Th1), but increased CD4+CD25+Foxp3+ T cell (Treg) contents. Importantly, Rapa-imDC administration ameliorated airway obliteration symptoms and CD4+ and CD8+ T cell infiltration. Furthermore, the proinflammatory factor levels of IL-6, TNF-α, IFN-x03B3; and IL-17 were decreased, concomitant with the upregulation of immunosuppressive cytokines IL-10 and TGF-β1. Further analysis confirmed that Rapa-imDC treatment attenuated the amounts of infiltrated IL-17+CD4+ T cells (Th17 cells) and Th1 cells, but increased Treg contents in the spleens of recipients. CONCLUSIONS: This research may corroborate a protective role of Rapa-imDCs in OB by regulating the balance between effector T cells and Tregs, suggesting a potential applicable strategy to treat OB after lung transplantation.
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Authors | Ming Dong, Xin Wang, Jie Liu, Yu-Xia Zhao, Xing-Long Chen, Ke-Qiu Li, Guang Li |
Journal | International archives of allergy and immunology
(Int Arch Allergy Immunol)
Vol. 167
Issue 3
Pg. 177-85
( 2015)
ISSN: 1423-0097 [Electronic] Switzerland |
PMID | 26302996
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 S. Karger AG, Basel. |
Chemical References |
- Cytokines
- Immunosuppressive Agents
- Inflammation Mediators
- Sirolimus
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Topics |
- Allografts
- Animals
- Antigen Presentation
(immunology)
- Bronchiolitis Obliterans
(drug therapy, immunology, pathology)
- Cytokines
(metabolism)
- Dendritic Cells
(drug effects, immunology, metabolism)
- Disease Models, Animal
- Graft Rejection
(drug therapy, immunology)
- Immunomodulation
(drug effects)
- Immunophenotyping
- Immunosuppressive Agents
(pharmacology)
- Inflammation Mediators
(metabolism)
- Lymphocyte Activation
- Male
- Rats
- Sirolimus
(pharmacology)
- T-Lymphocyte Subsets
(immunology, metabolism)
- T-Lymphocytes, Regulatory
(immunology, metabolism)
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