Gene transfer of RANTES elicits autoimmune renal injury in MRL-Fas(1pr) mice

Kidney Int. 1998 Jun;53(6):1631-41. doi: 10.1046/j.1523-1755.1998.00911.x.


We report that the beta-chemokine RANTES, a chemoattractant for macrophages and T cells, is up-regulated in the MRL-Fas(1pr) kidney prior to injury, but not normal kidneys (MRL-++, C3H-++) and increases with progressive injury. Furthermore, we establish an association between RANTES expression in the kidney and renal damage using a gene transfer approach. Tubular epithelial cells genetically modified to secrete RANTES infused under the renal capsule incites interstitial nephritis in MRL-Fas(1pr), but not MRL-++ or C3H-++ mice. RANTES recruits predominantly macrophages (M phi) and CD4+ and CD8+ T cells. In contrast, gene transfer of CSF-1, another molecule up-regulated simultaneously with RANTES in MRL-Fas(1pr) kidneys, promotes the influx of M phi, CD4+ T cells and the unique double-negative (DN) T cells (CD4-, CD8-), which are prominent in diseased MRL-Fas(1pr) kidneys. Thus, RANTES and CSF-1 recruit distinct T cell populations into the MRL-Fas(1pr) kidney. In addition, delivery of RANTES and CSF-1 into the kidney of MRL-Fas(1pr) mice causes an additive increase in pathology. We suggest that the complementary recruitment of T cell populations by RANTES (CD4, CD8) and CSF-1 (CD4, DN) promotes autoimmune nephritis in MRL-Fas(1pr) mice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology
  • CD4 Antigens / analysis
  • CD8 Antigens / analysis
  • Chemokine CCL5 / genetics*
  • Chemokine CCL5 / pharmacology
  • Gene Transfer Techniques*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / genetics*
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred MRL lpr / genetics*
  • Mice, Inbred MRL lpr / metabolism
  • RNA, Messenger / metabolism
  • T-Lymphocytes / immunology


  • CD4 Antigens
  • CD8 Antigens
  • Chemokine CCL5
  • RNA, Messenger
  • Macrophage Colony-Stimulating Factor