title: Activated CD4+ T cells target mesangial antigens and initiate glomerulonephritis.
abstract: OBJECTIVE
  The role of kidney infiltrating T cells in the pathology of lupus nephritis is unclear. This study was undertaken to investigate whether CD4+ T cell responses to a surrogate mesangial antigen can initiate glomerulonephritis.
  
  
  METHODS
  Ovalbumin (OVA) was deposited in the glomerular mesangium of C57BL/6 (B6) mice using anti-α8-integrin immunoliposomes (α8ILs). This was followed by injection of activated OVA-reactive CD4+ transgenic OT2 T cells. Trafficking of antigen-specific OT2 T cells to kidneys and lymph nodes was studied by flow cytometry. Glomerular pathology and immune cell infiltration was characterized by immunostaining. Role of CCR2 deficiency on T cell-mediated glomerulonephritis was investigated using B6.ccr2(-/-) mice.
  
  
  RESULTS
  α8ILs delivered OVA specifically to the renal glomeruli. Adoptively transferred OT2 T cells preferentially accumulated in renal lymph nodes and in the renal cortex. Kidneys showed glomerular inflammation with recruitment of endogenous T cells, dendritic cells and macrophages. T cell-mediated inflammation induced mesangial cell activation and an increase in glomerular MCP1 and fibronectin. The formation of inflammatory foci was driven by Ly6C monocytes and was CCR2 dependent.
  
  
  CONCLUSIONS
  The findings from this study show that T cells reactive with antigens in the mesangium are sufficient to initiate glomerular pathology. Antigen-specific CD4 T cells act by inducing glomerular MCP1 production which mediates recruitment of inflammatory monocytes resulting in glomerulonephritis. Thus, down-modulation of T cell responses within the kidneys of lupus patients will be a beneficial therapeutic approach.
authors.affiliation: Center for Immunity, Inflammation, and Regenerative Medicine, Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, Va 22908, USA.
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Scindia
authors.forename: Dominika
authors.initials: D
authors.lastname: Nackiewicz
authors.forename: Paromita
authors.initials: P
authors.lastname: Dey
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szymula
authors.forename: Amandeep
authors.initials: A
authors.lastname: Bajwa
authors.forename: Diane L
authors.initials: DL
authors.lastname: Rosin
authors.forename: W Kline
authors.initials: WK
authors.lastname: Bolton
authors.forename: Mark D
authors.initials: MD
authors.lastname: Okusa
authors.forename: Umesh
authors.initials: U
authors.lastname: Deshmukh
authors.forename: Harini
authors.initials: H
authors.lastname: Bagavant
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D050527:Mesangial Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000941:Antigens