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.
Lihua Bao, Mark Haas, Jeffrey Pippin, Ying Wang, Takashi Miwa, Anthony Chang, Andrew W. Minto, Miglena Petkova, Guilin Qiao, Wen-Chao Song, Charles E. Alpers, Jian Zhang, Stuart J. Shankland, Richard J. Quigg
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