CD4+ T Lymphocytes, especially Th2 cells, contribute to the progress of renal fibrosis.
BACKGROUND
Renal tubulointerstitial fibrosis is the final common stage of renal failure. CD4+ T lymphocyte recruitment and activation after injury could be the very important early event that mediates the onset of renal fibrogenesis. But the role of CD4+ T lymphocytes in renal fibrosis is controversial and its cellular mechanism needs to be further investigated.


METHODS
Biopsy specimens were from patients with minimal-change or IgA nephropathy. Mouse renal fibrosis was induced by unilateral ureteral obstruction (UUO). CD4+ T lymphocytes of wild BALB/c mice were depleted with anti-CD4 antibody. BALB/c Nu/Nu mice were reconstituted with polarized Th1 or Th2 cells by tail vein injection.


RESULTS
Our study demonstrated that massive CD4+ T lymphocytes infiltrated fibrotic kidneys of patients. The depletion of CD4+ T lymphocytes inhibited UUO-induced mouse renal fibrosis. In the process of UUO-induced renal fibrosis, the ratios of Th2/Th1 increased with time. Results have also shown that Th2-reconstituted mice developed renal fibrosis more easily than Th1-reconstituted mice, which manifested by interstitial expansion and collagen deposition, higher expression of α-SMA and vimentin and increased expression of fibronectin, TGF-β and collagen I. We also found that CD4+ T cells from Th1-reconstitued mice tended to secrete IL-4 and IL-13 Th2-like cytokines.


CONCLUSIONS
In conclusion, our study demonstrated the importance of CD4+ T lymphocytes in renal fibrosis and gave the first direct evidence that Th2 cells play a pivotal role in UUO-induced renal fibrosis. Inhibition of CD4+ T lymphocyte differentiation to Th2 would be a potential therapeutic intervention to prevent renal fibrosis.
Division of Nephrology, Department of Internal Medicine, Tongji Hospital, PR China.
Lili
L
Liu
Pei
P
Kou
Qiao
Q
Zeng
Guangchang
G
Pei
Yueqiang
Y
Li
Huifang
H
Liang
Gang
G
Xu
Sheng
S
Chen
D000818:Animals; D001706:Biopsy; D002454:Cell Differentiation / Q000276:immunology; D004195:Disease Models, Animal; D005355:Fibrosis / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D005922:Glomerulonephritis, IGA / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000473:pathology*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009402:Nephrosis, Lipoid / Q000276:immunology / Q000473:pathology*; D051436:Renal Insufficiency, Chronic / Q000276:immunology / Q000473:pathology*; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology*; D014517:Ureteral Obstruction / Q000276:immunology / Q000473:pathology