title: Decreased percentages of regulatory T cells are necessary to activate Th1-Th17-Th22 responses during acute rejection of the peripheral nerve xenotransplantation in mice.
abstract: BACKGROUND
  T cells have major functions in the initiation and perpetuation of nerve graft rejection. Our study aimed to investigate the function of regulatory T cells (Treg)-Th1-Th17-Th22 cells in the rejection of peripheral nerve xenotransplantation.
  
  
  METHODS
  Adult male C57 BL/6 mice were used as the recipient for nerve xenotransplantation, and Sprague-Dawley rats were used as the donor. These nerve xenotransplanted mice were used as the experimental groups, and those that received autograft transplant were chosen as the control group. All of the animals were pretreated with interferon (IFN)-γ, interleukin (IL)-17, and IL-22 before the experiment was conducted. The percentages of spleen Treg-Th1-Th17-Th22 cells were evaluated by flow cytometry 1, 3, 7, 14, and 28 days after transplantation. Serum levels of IFN-γ, IL-17, and IL-22 were assessed by enzyme-linked immunosorbent assay. Statistical analysis was performed by Wilcoxon rank sum and Spearman correlation test.
  
  
  RESULTS
  During acute rejection, the percentages of Th1-Th17-Th22 cells in the spleen and serum IFN-γ, IL-17, and IL-22 levels in the experimental group increased compared with those in the control group. By contrast, CD4CD25Foxp3 T cell level decreased. The rejection of xenograft was significantly prevented after the mice were treated with IL-17-neutralizing, IL-22-neutralizing, and IFN-γ-neutralizing antibodies. Moreover, the percentage of CD4CD25Foxp3 Treg was negatively correlated with the percentages of Th1-Th17-Th22 cells and levels of IL-17, IL-22, and IFN-γ.
  
  
  CONCLUSIONS
  These results suggested that the Treg-Th1-Th17-Th22 cells involved in xenotransplant rejection and imbalance between Tregs and Th1-Th17-Th22 cells contribute to the acute rejection of peripheral nerve xenotransplant.
authors.affiliation: 1 Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China. 2 The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, China. 3 Department of Orthopedic Surgery, Jilin University, Third Hospital (China-Japan Union Hospital) of Jilin University, Changchun, China. 4 Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China. 5 Formerly Department of Functional Neurology and Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China; currently Department of Neurology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangdong Neuroscience Institute, Guangzhou, China 6 Address correspondence to: Yanwu Guo, Ph.D., Department of Neurosurgery, Zhujiang Hospital, National Key Clinic Specialty, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Southern Medical University, 253 Gongye Road, Guangzhou, 510282, China. 7 Address correspondence to: Bing Qin, Ph.D., Department of Neurology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangdong Neuroscience Institute, Guangzhou, 510080, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Chai
authors.forename: Lujun
authors.initials: L
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.forename: Yanwu
authors.initials: Y
authors.lastname: Guo
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Xulong
authors.initials: X
authors.lastname: Fan
authors.forename: Bolin
authors.initials: B
authors.lastname: Wu
authors.forename: Shan
authors.initials: S
authors.lastname: Xue
authors.forename: Yingqian
authors.initials: Y
authors.lastname: Cai
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Jiang
authors.forename: Bing
authors.initials: B
authors.lastname: Qin
authors.forename: Shizhong
authors.initials: S
authors.lastname: Zhang
authors.forename: Yiquan
authors.initials: Y
authors.lastname: Ke
mesh_terms: D000818:Animals; D002452:Cell Count; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006084:Graft Rejection; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D020381:Interleukin-17 / Q000097:blood; D007378:Interleukins / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000637:transplantation*; D010525:Peripheral Nerves / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D018417:Th1 Cells / Q000166:cytology*; D058504:Th17 Cells / Q000166:cytology*; D014183:Transplantation, Heterologous; D000097043:Interleukin-22
chemical_list: D051858:Forkhead Transcription Factors; D007371:Interferon-gamma; D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22; C498833:Foxp3 protein, mouse