Focal and segmental glomerulosclerosis induced in mice lacking  decay-accelerating factor in T cells.
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.
Bao
Lihua
L
University of Chicago, Illinois, 60637, USA. lbao@medicine.bsd.uchicago.edu
Haas
Mark
M
Pippin
Jeffrey
J
Wang
Ying
Y
Miwa
Takashi
T
Chang
Anthony
A
Minto
Andrew W
AW
Petkova
Miglena
M
Qiao
Guilin
G
Song
Wen-Chao
WC
Alpers
Charles E
CE
Zhang
Jian
J
Shankland
Stuart J
SJ
Quigg
Richard J
RJ
D000419:Albuminuria / Q000139:chemically induced / Q000652:urine; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D018958:CD55 Antigens / Q000235:genetics*; D018957:CD59 Antigens / Q000235:genetics; D002465:Cell Movement / Q000276:immunology; D004195:Disease Models, Animal; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D007111:Immunity, Cellular / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D016513:Mice, SCID; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D050199:Podocytes / Q000276:immunology; D012756:Sheep; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation
D000906:Antibodies; D018958:CD55 Antigens; D018957:CD59 Antigens; C539311:CD59a protein, mouse; D007074:Immunoglobulin G; C521184:decay-accelerating factor 1, mouse