An anti-CD5 monoclonal antibody ameliorates proteinuria and glomerular lesions in rat mesangioproliferative glomerulonephritis

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.