title: Rapamycin Combined with Immature Dendritic Cells Attenuates Obliterative Bronchiolitis in Trachea Allograft Rats by Regulating the Balance of Regulatory and Effector T Cells.
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.
authors: Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Ming
authors: M
authors: Dong
authors: Xin
authors: X
authors: Wang
authors: Jie
authors: J
authors: Liu
authors: Yu-Xia
authors: YX
authors: Zhao
authors: Xing-Long
authors: XL
authors: Chen
authors: Ke-Qiu
authors: KQ
authors: Li
authors: Guang
authors: G
authors: Li
mesh_terms: D064591:Allografts; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001989:Bronchiolitis Obliterans / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology; D056747:Immunomodulation / Q000187:drug effects*; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D051381:Rats; D020123:Sirolimus / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D020123:Sirolimus