title: Near-term anti-CD25 monoclonal antibody administration protects murine liver from ischemia-reperfusion injury due to reduced numbers of CD4+ T cells.
abstract: BACKGROUND
  CD4(+) T cell is acknowledged as a key factor in the initiation phase of liver ischemia reperfusion injury. The purpose of current study is to demonstrate the effect of antecedent near-term anti-CD25 monoclonal antibody treatment on IR-induced liver injury by modulation of CD4(+) T cells.
  
  
  METHODS
  70% liver warm IR was induced in male C57BL/6 mice after anti-CD25 mAb or non-specific IgG administration. Liver function, histological damage, in vitro Proliferation, FACS, cytokine production, and immunofluorescence were assessed to evaluate the impact of antecedent near-term PC61 treatment on IR-induced liver injury.
  
  
  RESULTS
  After 70% liver ischemia, mice preconditioned with PC61 displayed significantly preserved liver function as characterized by less histological damage and reduced serum enzymes level. Mechanistic studies revealed that the protection effect of anti-CD25 mAb was associated with ameliorated intrahepatic inflammatory milieu and reduced CD4(+) T lymphocytes as manifested by the decrease of proinflammatory cytokine production (less expression of TNF-α, IFN-γ, IL-2, and IL-6) and the lower CD4/CD8 proportion.
  
  
  CONCLUSIONS
  Our results provide first line of evidence indicating that near-term treatment with anti-CD25 monoclonal antibody might provide protection for livers against IR-induced injury by reducing CD4(+) T cells, but not influencing functional Treg population. Therefore, our results demonstrate a potential function of anti-CD25 monoclonal antibody which was neglected in the past, and may be helpful in various clinical conditions, particularly in liver and kidney transplantations.
authors.affiliation: Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zhiren
authors.initials: Z
authors.lastname: Fu
authors.affiliation: National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, China.
authors.forename: Quanxing
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D015870:Gene Expression; D056747:Immunomodulation; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D061251:Primary Cell Culture; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D000093242:Interleukin-6 Inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D007371:Interferon-gamma; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C584092:PC61 monoclonal antibody