Focal and segmental glomerulosclerosis induced in mice lacking decay-accelerating factor in T cells

J Clin Invest. 2009 May;119(5):1264-74. doi: 10.1172/JCI36000.


Heritable and acquired diseases of podocytes can result in focal and segmental glomerulosclerosis (FSGS). We modeled FSGS by passively transferring mouse podocyte-specific sheep Abs into BALB/c mice. BALB/c mice deficient in the key complement regulator, decay-accelerating factor (DAF), but not WT or CD59-deficient BALB/c mice developed histological and ultrastructural features of FSGS, marked albuminuria, periglomerular monocytic and T cell inflammation, and enhanced T cell reactivity to sheep IgG. All of these findings, which are characteristic of FSGS, were substantially reduced by depleting CD4+ T cells from Daf(-/-) mice. Furthermore, WT kidneys transplanted into Daf(-/-) recipients and kidneys of DAF-sufficient but T cell-deficient Balb/(cnu/nu) mice reconstituted with Daf(-/-) T cells developed FSGS. In contrast, DAF-deficient kidneys in WT hosts and Balb/(cnu/nu) mice reconstituted with DAF-sufficient T cells did not develop FSGS. Thus, we have described what we believe to be a novel mouse model of FSGS attributable to DAF-deficient T cell immune responses. These findings add to growing evidence that complement-derived signals shape T cell responses, since T cells that recognize sheep Abs bound to podocytes can lead to cellular injury and development of FSGS.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Albuminuria / chemically induced
  • Albuminuria / urine
  • Animals
  • Antibodies / immunology
  • Antibody Formation / immunology
  • CD55 Antigens / genetics*
  • CD59 Antigens / genetics
  • Cell Movement / immunology
  • Disease Models, Animal*
  • Glomerulosclerosis, Focal Segmental / chemically induced
  • Glomerulosclerosis, Focal Segmental / immunology*
  • Glomerulosclerosis, Focal Segmental / pathology
  • Immunity, Cellular / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / pathology
  • Kidney Transplantation
  • Lymphocyte Activation / immunology
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Mice, SCID
  • Monocytes / cytology
  • Monocytes / immunology
  • Podocytes / immunology
  • Sheep
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation


  • Antibodies
  • CD55 Antigens
  • CD59 Antigens
  • CD59a protein, mouse
  • Immunoglobulin G
  • decay-accelerating factor 1, mouse