Renal tubular epithelial expression of the coinhibitory molecule B7-DC (programmed death-1 ligand).
BACKGROUND
Renal tubular epithelial cells (TECs) function as antigen-presenting cells because they constitutively express MHC class II molecules and have the ability to present peptide antigen to CD4+T cells. However, the costimulatory signals provided by TECs for optimal T-cell activation have not been fully characterized. Increasing recognition of the importance of B7 dendritic cells (B7-DC) in immunoregulation raises the question of whether B7-DC is expressed on TECs and is involved in regulating TEC function.


METHODS
B7-DC on cultured human and murine TECs was detected by flow cytometry in vitro. Immunohistochemistry was performed on human kidney biopsies. Coculture experiments were performed to confirm the role of TEC-related B7-DC in regulating CD4+T-cell activation.


RESULTS
Data revealed that B7-DC is specifically expressed on TECs with inflammatory factor induced and diseased human kidney samples, including chronic glomerulonephritis, lupus nephritis, tubulointerstitial nephritis and renal cell carcinoma. B7-DC was a strong inhibitor of CD4+T-cell activation, as assessed by increased cytokine (interferon-gamma and interleukin-2) production and enhanced levels of T-cell activation marker CD69 in the presence of its blocking antibody. Blocking B7-DC/PD-1 enhanced antigen presentation. B7-DC is especially well expressed on TECs of diseased kidney samples and significantly down-regulates T-cell activation.


CONCLUSIONS
We speculate that B7-DC might play an important role in maintaining peripheral tolerance, and in protecting the epithelium from immune-mediated tubulointerstitial injury.
Zhang
Jingbo
J
Department of Nephrology, Xin-Qiao Hospital, Third Military Medical University, Chongqing, P.R. China.
Chen
Yongwen
Y
Li
Jingyi
J
Zhang
Rui
R
Wu
Yi
Y
Zou
Liyun
L
Zhao
Tingting
T
Zhang
Xiaoping
X
Han
Junfeng
J
Chen
An
A
Wu
Yuzhang
Y
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D018122:B7-1 Antigen / Q000032:analysis / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000502:physiology*; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D007684:Kidney Tubules / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D061026:Programmed Cell Death 1 Receptor
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma