Expression of B7-H1 in inflammatory renal tubular epithelial cells.
BACKGROUND
Renal tubular epithelial cells (TECs) function as antigen-presenting cells (APCs) as they constitutively express MHC-II molecules and have the capacity to present peptide antigen to T cells. Nevertheless, co-stimulatory signals provided by TECs for regulating T cell activation have not been fully characterized. We therefore investigated the expression of B7-H1, a member of the B7 superfamily, on TECs under normal or pathologic conditions in vivo and analyzed the regulation and functional role of it after proinflammatory factors treatment in vitro.


METHODS
Immunohistological staining for B7-H1 on cryostat sections of core needle biopsies from patients with different renal diseases was examined. Furthermore, we also detected B7-H1 protein expression on cultured human TECs stimulated by various inflammatory factors and performed TEC/T-cell co-cultured experiment to determine TEC-associated B7-H1 in regulating CD4+ T cell activation as well as antigen presentation.


RESULTS
Significant B7-H1 protein was detected in TECs of diseased renal samples. Although the presence of B7-H1 does not have any correlation with clinicopathological variables, marked B7-H1 expression on sections without interstitial inflammation revealed that B7-H1 has some protective function. In vitro, the expression of B7-H1 on TECs was increased after TECs were stimulated with IL-1alpha, LPS, TNF-alpha, IFN-gamma or anti-CD40. Co-cultured experiments revealed that TEC-related B7-H1 was identified as a strong inhibitor of CD4+ T-cell activation as assessed by increased cytokine production (interleukin-2 and interferon-gamma) and expression levels of the T cell activation marker (CD69) in the presence of a neutralizing antibody against B7-H1 (clone MIH1). Interestingly, IL-2 production by C10 T cells after antigen presentation by murine TECs was also enhanced when the B7-H1/PD-1 pathway was interrupted.


CONCLUSIONS
This study clearly shows that B7-H1 is an inducible renal tubular epithelial antigen that inhibits T cell activation. It is speculated that B7-H1/PD-1 pathway might play a role in protecting tubular epithelium from immune-mediated damage and active delivery of the B7-H1 inhibitory signal represents a novel therapeutic strategy in autoimmune renal diseases.
Chen
Yongwen
Y
Institute of Immunology, PLA, The Third Military Medical University, Chongqing, PR China.
Zhang
Jingbo
J
Li
Jingyi
J
Zou
Liyun
L
Zhao
Tingting
T
Tang
Yan
Y
Wu
Yuzhang
Y
D000818:Animals; D000941:Antigens / Q000096:biosynthesis; D015703:Antigens, CD; D000954:Antigens, Surface / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism*; D060890:B7-H1 Antigen; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009393:Nephritis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010455:Peptides / Q000378:metabolism*; D061026:Programmed Cell Death 1 Receptor; D013601:T-Lymphocytes
D000941:Antigens; D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; D016207:Cytokines; D008562:Membrane Glycoproteins; C105992:PDCD1 protein, human; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor