Pivotal role of CD4+ T cells in renal fibrosis following ureteric obstruction.
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.
Tapmeier
Thomas T
TT
MRC Centre for Transplantation, King's College London School of Medicine at Guy's, King's and St Thomas' Hospitals, London, UK.
Fearn
Amy
A
Brown
Kathryn
K
Chowdhury
Paramit
P
Sacks
Steven H
SH
Sheerin
Neil S
NS
Wong
Wilson
W
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D005355:Fibrosis / Q000209:etiology* / Q000517:prevention & control; D018398:Homeodomain Proteins / Q000235:genetics; D007674:Kidney Diseases / Q000209:etiology* / Q000276:immunology; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D014517:Ureteral Obstruction / Q000150:complications* / Q000473:pathology
D018398:Homeodomain Proteins; C064658:RAG-1 protein; D003094:Collagen