Journal
KIDNEY INTERNATIONAL
Volume 58, Issue 1, Pages 100-114Publisher
BLACKWELL SCIENCE INC
DOI: 10.1046/j.1523-1755.2000.00145.x
Keywords
T lymphocyte; macrophage; Thy 1.1 glomerulonephritis; kidney lesions; proteinuria; nephropathy; inflammation
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Background. Increased numbers of lymphocytes have been identified in biopsy specimens of human mesangial proliferative glomerulonephritis (GN). However, the causal relationship between infiltrating T lymphocytes and mesangial changes in mesangial proliferative GN has not been previously evaluated. In this study, we elucidated the role of lymphocytes in the development of mesangial proliferative GN. Methods . Immunohistological and flow cytometric analyses as well as a reverse transcription-polymerase chain reaction (RT-PCR) studies were performed in monoclonal antibody (mAb) 1-22-3-induced Thy 1.1 GN. To elucidate the role of these lymphocytes, depletion studies were carried out using anti-CD8 mAb (OX-8), which depletes both CD8(+) T lymphocytes and natural killer (NK) cells and anti-CDS mAb (OX-19), which depletes both CD4(+) and CD8(+) T lymphocytes. Results. Immunofluorescence (IF) studies revealed that NK cells and CD4(+) T lymphocytes were recruited into glomeruli. Glomerular mRNA expression for interferon-gamma, interleukin-2 (IL-2), IL-10, and perforin increased after induction of GN. Increased expressions of several chemokines, which have the potential to attract lymphocytes, were also detected. Anti-CD8 mAb treatment completely prevented the recruitment of NK cells: however, it had no protective effect on proteinuria and mesangial injury. By contrast, anti-CDS mAb treatment suppressed the recruitment of CD4(+) T lymphocytes into glomeruli and reduced proteinuria (60.4 +/- 25.7 vs. 120.0 +/- 32.3 mg/day, P < 0.05) and mesangial changes evaluated by total number of cells in glomeruli (63.2 +/- 6.0 vs. 81.4 +/- 5.9, P < 0.01) and alpha-smooth muscle actin staining score (1.4 +/- 0.2 vs. 2.2 +/- 0.4, P < 0.01) on day 14 after induction of GN. mRNA expression for IL-2 was significantly reduced by OX-19 treatment. Conclusion. T lymphocytes participate in the development of mesangial proliferative GN.
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