title: Role of donor-specific regulatory T cells in long-term acceptance of rat hind limb allograft.
abstract: BACKGROUND
  Vascularized bone marrow transplantation (VBMT) is widely accepted as an efficient means of establishing chimerism and inducing tolerance. However, the mechanism underlying is poorly understood. Recently, regulatory T cells (Tregs) have been shown to play an important role in regulating immune responses to allogeneic antigens. In this study, we explored the role of Tregs in the induction of tolerance in an allogeneic hind limb transplantation model.
  
  
  RESULTS
  Forty-eight Lewis rats were divided into 6 groups. They received isografts and allografts from Brown-Norway hind limbs. Recipients in groups 1 and 2 received isografts and those in the other groups received allografts. The bone components of donor limbs were kept intact in groups 1, 3, and 5 but removed before transplantation into groups 2, 4, and 6. Tapered cyclosporin A (CsA) was administered to recipients in groups 5 and 6 after transplantation. During the 100-day observation period, all isografts survived, but the allografts in groups 3 and 4 were rejected within 8 to 12 days. CsA-treated intact allografts survived rejection-free for more than 100 days, and CsA-treated allografts lacking bone elements were rejected within 2 months. Stable peripheral chimerism and myeloid chimerism were observed in group 5. Declining peripheral chimerism and a lack of myeloid chimerism were observed in group 6. Donor-specific Tregs were exclusively detected in both peripheral blood and in the spleens of long-term recipient rats in group 5, with an increased FoxP3 mRNA expression in the allografts. This was further demonstrated to be responsible for donor-specific hyporeactivity by in vitro one-way mixed lymphocyte reaction (MLR).
  
  
  CONCLUSIONS
  Bone components in the allogeneic hind limbs can induce myeloid chimerism and donor-specific Tregs may be essential to tolerance induction. The bone-removal hind limb model may be a suitable counterpart to the induction of tolerance in the study of limb transplantation.
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Yaojun
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zheng
authors.forename: Yunchuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Hu
authors.forename: Fu
authors.initials: F
authors.lastname: Han
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Dahai
authors.initials: D
authors.lastname: Hu
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology; D049109:Cell Proliferation; D046528:Chimerism; D005121:Extremities / Q000637:transplantation*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014019:Tissue Donors; D023001:Transplantation Tolerance / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat