Pivotal role of CD4+ T cells in renal fibrosis following ureteric obstruction

Thomas T. Tapmeier, Amy Fearn, Kathryn Brown, Paramit Chowdhury, Steven H. Sacks, Neil S. Sheerin, Wilson Wong

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81 Citations (Scopus)

Abstract

Tubulointerstitial fibrosis is a common consequence of a diverse range of kidney diseases that lead to end-stage renal failure. The degree of fibrosis is related to leukocyte infiltration. Here, we determined the role of different T cell populations on renal fibrosis in the well-characterized mouse model of unilateral ureteric obstruction. Depletion of CD4+ T cells in wild-type mice with a monoclonal antibody significantly reduced the amount of interstitial expansion and collagen deposition after 2 weeks of obstruction. Reconstitution of lymphopenic RAG knockout mice with purified CD4+ but not CD8+ T cells, prior to ureteric obstruction, resulted in a significant increase in interstitial expansion and collagen deposition. Wild-type mice had significantly greater interstitial expansion and collagen deposition compared with lymphopenic RAG/mice, following ureteric obstruction; however, macrophage infiltration was equivalent in all groups. Thus, our results suggest that renal injury with subsequent fibrosis is likely to be a multifactorial process, with different arms of the immune system involved at different stages. In this ureteric obstruction model, we found a critical role for CD4+ T cells in kidney fibrosis. These cells could be a potential target of therapeutic intervention to prevent excessive fibrosis and loss of function due to renal injury.

Original languageEnglish
Pages (from-to)351-362
Number of pages12
JournalKidney International
Volume78
Issue number4
DOIs
Publication statusPublished - Aug 2010
Externally publishedYes

Keywords

  • fibrosis
  • ureteric obstruction

Cite this

Tapmeier, T. T., Fearn, A., Brown, K., Chowdhury, P., Sacks, S. H., Sheerin, N. S., & Wong, W. (2010). Pivotal role of CD4+ T cells in renal fibrosis following ureteric obstruction. Kidney International, 78(4), 351-362. https://doi.org/10.1038/ki.2010.177