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- Title
Focal and segmental glomerulosclerosis induced in mice lacking decay-accelerating factor in T cells.
- Authors
Bao, Lihua; Haas, Mark; Pippin, Jeffrey; Ying Wang; Miwa, Takashi; Chang, Anthony; Minto, Andrew W.; Petkova, Miglena; Guilin Qiao; Wen-Chao Song; Alpers, Charles E.; Jian Zhang; Shankland, Stuart J.; Quigg, Richard J.; Wang, Ying; Qiao, Guilin; Song, Wen-Chao; Zhang, Jian
- Abstract
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.
- Subjects
MEDICAL research; LYMPHOCYTES; T cells; NEPHROLOGY; URINALYSIS; KIDNEY diseases
- Publication
Journal of Clinical Investigation, 2009, Vol 119, Issue 5, p1264
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI36000