Journal article
Focal and segmental glomerulosclerosis induced in mice lacking decay-accelerating factor in T cells
The Journal of clinical investigation, Vol.119(5), pp.1264-1274
05/01/2009
DOI: 10.1172/JCI36000
PMCID: PMC2673859
PMID: 19349693
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/c
nu/nu
mice reconstituted with
Daf
–/–
T cells developed FSGS. In contrast, DAF-deficient kidneys in WT hosts and
Balb/c
nu/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.
Details
- Title: Subtitle
- Focal and segmental glomerulosclerosis induced in mice lacking decay-accelerating factor in T cells
- Creators
- Lihua Bao - Section of Nephrology, University of Chicago, Chicago, Illinois, USAMark Haas - Johns Hopkins UniversityJeffrey Pippin - University of WashingtonYing Wang - Section of Nephrology, University of Chicago, Chicago, Illinois, USATakashi Miwa - University of PennsylvaniaAnthony Chang - University of Washington School of MedicineAndrew W Minto - Section of Nephrology, University of Chicago, Chicago, Illinois, USAMiglena Petkova - Section of Nephrology, University of Chicago, Chicago, Illinois, USAGuilin Qiao - Section of Nephrology, University of Chicago, Chicago, Illinois, USAWen-Chao Song - University of PennsylvaniaCharles E Alpers - University of Washington School of MedicineJian Zhang - Section of Nephrology, University of Chicago, Chicago, Illinois, USAStuart J Shankland - University of Washington School of MedicineRichard J Quigg - Section of Nephrology, University of Chicago, Chicago, Illinois, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.119(5), pp.1264-1274
- DOI
- 10.1172/JCI36000
- PMID
- 19349693
- PMCID
- PMC2673859
- NLM abbreviation
- J Clin Invest
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Publisher
- American Society for Clinical Investigation
- Language
- English
- Date published
- 05/01/2009
- Academic Unit
- Pathology
- Record Identifier
- 9984047741302771
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