| First Author | Bao L | Year | 2009 |
| Journal | J Clin Invest | Volume | 119 |
| Issue | 5 | Pages | 1264-74 |
| PubMed ID | 19349693 | Mgi Jnum | J:149592 |
| Mgi Id | MGI:3848733 | Doi | 10.1172/JCI36000 |
| Citation | Bao L, et al. (2009) Focal and segmental glomerulosclerosis induced in mice lacking decay-accelerating factor in T cells. J Clin Invest 119(5):1264-74 |
| abstractText | 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. |
