title: Aberrant recruitment and activation of T cells in diabetic nephropathy.
abstract: OBJECTIVE
  Recent evidence has shown that an inflammatory process is involved in the development and progression of diabetic nephropathy. This study examined the impact of activated intrarenal lymphocytes in this inflammatory process.
  
  
  METHODS
  We studied T cell recruitment in mice with streptozotocin (STZ)-induced diabetes by flow cytometry and immunohistochemistry. The kidney biopsy specimens from patients with type 2 diabetes mellitus and diabetic nephropathy were evaluated by immunohistochemistry.
  
  
  RESULTS
  In flow cytometry, intrarenal CD3+ T cells were significantly increased in proteinuric mice at 20 weeks after STZ injection. However, the population of T cells and B cells in diabetic spleen was not different from that of control mice. Immunohistochemistry also showed a marked infiltration of interstitial CD4+, CD8+ T cells in diabetic kidney. Interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) mRNA expression was significantly increased in diabetic mouse kidney compared with controls. Interestingly, flow cytometry analysis of kidney-derived mononuclear cells from diabetic mice showed significantly increased production of IFN-γ and TNF-α by CD3+ T cells. Type 2 diabetic patients also showed a marked increase in CD4+, CD8+ and CD20+ cells in interstitium, and the number of CD4+ and CD20+ cells correlated with the amount of proteinuria.
  
  
  CONCLUSIONS
  Our results clearly showed that aberrant intrarenal infiltration and the activation of T cells in interstitium are the underlying immunopathological mechanisms of diabetic kidney injury.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Moon
authors.forename: Kyung-Hwan
authors.initials: KH
authors.lastname: Jeong
authors.forename: Tae-Won
authors.initials: TW
authors.lastname: Lee
authors.forename: Chun-Gyoo
authors.initials: CG
authors.lastname: Ihm
authors.forename: Sung Jig
authors.initials: SJ
authors.lastname: Lim
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D018951:Antigens, CD20 / Q000378:metabolism; D001402:B-Lymphocytes; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000150:complications* / Q000276:immunology; D003928:Diabetic Nephropathies / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011507:Proteinuria / Q000209:etiology; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D018709:Statistics, Nonparametric; D013311:Streptozocin; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018951:Antigens, CD20; D017252:CD3 Complex; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013311:Streptozocin; D007371:Interferon-gamma