title: 4-1BB-mediated signals confer protection against folic acid-induced nephrotoxicity.
abstract: BACKGROUND
  The role of co-stimulatory molecules in renal diseases has been previously examined, however, little is known about the role of 4-1BB in the context of renal diseases resulting from nonimmune-mediated tubulointerstitial fibrosis. Folic acid induced Nephrotoxicity (FAN) in mice was used to explore the role of 4-1BB in this setting.
  
  
  METHODS
  CD1 mice were treated with folic acid and kidneys subsequently examined using histochemistry, in addition to defining T cell profiles and evaluating renal function. Increased CD3+ and CD4+ T lymphocytes present in blood and spleen at day 3 suggested immunopathological reactions during the early stages of FAN and decreased CD3+ and CD4+ T lymphocytes on day 14 were characteristic of an immunocompromised state observed during the late stages of FAN.
  
  
  RESULTS
  After 14 days of co-treatment with agonistic anti-4-1BB monoclonal antibodies, renal tubulointerstitial lesions were reduced. Renal function was improved, with Bun scores decreasing (p<0.01) and sCr levels decreasing (p<0.01). CD3+ and CD4+ T lymphocytes levels were increased during the early stages of disease in FA treated mice and reduced to the normal level in the 4-1BB-treated mice. CD3+ and CD4+ T lymphocytes levels were decreased in FA treated mice and returned to baseline in the 4-1BB-treated mice during later stages.
  
  
  CONCLUSIONS
  Data presented in this report demonstrated that 4-1BB signals had immunoregulatory effects that attenuated early immune-mediated pathology and reversed the immunocompromised state observed during the later stages of disease.
authors: Children Hospital & Medical Bio-tech Institute Affiliated to Soochow University, #303 Jingde Road, Suzhou Jiangsu 215003, China. xiaozhonglicn@yeah.net
authors: Xiaozhong
authors: X
authors: Li
authors: Jihong
authors: J
authors: Dai
authors: Yuhua
authors: Y
authors: Qiu
authors: Xueguang
authors: X
authors: Zhang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004195:Disease Models, Animal; D005355:Fibrosis; D005492:Folic Acid / Q000009:adverse effects*; D007107:Immune System / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013601:T-Lymphocytes / Q000473:pathology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000819:agonists / Q000187:drug effects / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D005492:Folic Acid