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

Yohei Ikezumi, Hiroshi Kawachi, Shinichi Toyabe, Makoto Uchiyama, Fujio Shimizu

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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. Method: Immunohistological and flow cytometric analyses as well as a reverse transcription-polymerase chain reaction (RTPCR) 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-CD5 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-γ 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-CD5 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 α- 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.

Original languageEnglish
Pages (from-to)100-114
Number of pages15
JournalKidney International
Volume58
Issue number1
DOIs
Publication statusPublished - 01-01-2000

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Glomerulonephritis
Proteinuria
Monoclonal Antibodies
T-Lymphocytes
Natural Killer Cells
Interleukin-2
Lymphocytes
Lymphocyte Depletion
Perforin
Messenger RNA
Lymphocyte Count
Chemokines
Interleukin-10
Interferons
Reverse Transcription
Fluorescent Antibody Technique
Smooth Muscle
Actins
Therapeutics
Cell Count

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Ikezumi, Yohei ; Kawachi, Hiroshi ; Toyabe, Shinichi ; Uchiyama, Makoto ; Shimizu, Fujio. / An anti-CD5 monoclonal antibody ameliorates proteinuria and glomerular lesions in rat mesangioproliferative glomerulonephritis. In: Kidney International. 2000 ; Vol. 58, No. 1. pp. 100-114.
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abstract = "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. Method: Immunohistological and flow cytometric analyses as well as a reverse transcription-polymerase chain reaction (RTPCR) 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-CD5 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-γ 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-CD5 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 α- 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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An anti-CD5 monoclonal antibody ameliorates proteinuria and glomerular lesions in rat mesangioproliferative glomerulonephritis. / Ikezumi, Yohei; Kawachi, Hiroshi; Toyabe, Shinichi; Uchiyama, Makoto; Shimizu, Fujio.

In: Kidney International, Vol. 58, No. 1, 01.01.2000, p. 100-114.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An anti-CD5 monoclonal antibody ameliorates proteinuria and glomerular lesions in rat mesangioproliferative glomerulonephritis

AU - Ikezumi, Yohei

AU - Kawachi, Hiroshi

AU - Toyabe, Shinichi

AU - Uchiyama, Makoto

AU - Shimizu, Fujio

PY - 2000/1/1

Y1 - 2000/1/1

N2 - 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. Method: Immunohistological and flow cytometric analyses as well as a reverse transcription-polymerase chain reaction (RTPCR) 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-CD5 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-γ 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-CD5 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 α- 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.

AB - 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. Method: Immunohistological and flow cytometric analyses as well as a reverse transcription-polymerase chain reaction (RTPCR) 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-CD5 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-γ 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-CD5 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 α- 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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