Study for the role of B7 costimulatory molecule expressed in the tubular epithelial cells in the development of tubulointerstitial lesions

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 11671037
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Okayama University
• Principal Investigator: YAMASAKI Yasushi Okayama University, Hospital, Lecturer, 医学部・附属病院, 講師 (20304347)
• Co-Investigator(Kenkyū-buntansha): YAMAMURA Masahiro Okayama University, Graduate School of Medicine and Dentistry, Associate Professor, 大学院・医歯学総合研究科, 助教授 (80252956) ; MAKINO Hirofumi Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (50165685)
• Project Period (FY): 1999 – 2000
• Keywords: B7-1 / interstitial nephritis / MRL / lpr model / transgenic mice

Research Abstract

Tubulointerstitial lesion is characteristic for progressive renal diseases. In order to investigate the significance of T-cell costimulatory factor, B7-1 expression in tubular epithelial cells in the course of progressive glomerular diseases, we utilized MRL/lpr model, which is well-known as a spontaneous lupus nephritis model. We established the transgenic mice expressing B7-1 in the renal proximal tubules specifically and backcrossed onto MRL/lpr/lpr mice by 5 generations to produce B7-1 transgenic mice in the background of MRL/lpr/lpr. MRL/lpr/lpr-B7(+) mice developed severe glomerulonephritis with immune complex deposition in accordance to elevation of anti-double strand DNA antibody titer as well as MRL/lpr/lpr-B7(-) mice. The titer of anti-ds DNA antibody and the severelity of glomerulonephritis in the MRL/lpr/lpr-B7(+) mice were similar as compared with those in the MRL/lpr/lpr-B7(-) mice. However, mononuclear cell infiltration in the tubulointerstitium in the MRL/lpr/lpr-B7(+) mice was markedly increased in association with tubular epithelial cell damages. The majority of the infiltrates were CD4+ and CD8+ T cells, and particularly the increase of CD8+ T-cell infiltrates was significant. These data suggest that overexpression of B7-1 in the proximal tubular epithelial cells activate the infiltrating T cells in the course of progressive glomerular disease and might induce the cytotoxic T-cell reaction against tubular epithelial cells. In conclusion, tubular epithelial cells play an important role in the development of tubulointerstitial lesions and the expression of B7 costimulatory molecule in the tubules may accelerate T cell-mediated immune reaction.