Programmed death 1 and its ligands do not limit experimental foreign antigen-induced immune complex glomerulonephritis

Joshua Ooi, Ming Li, Katerina Kourkoutzelos, Hideo Yagita, Miyuki Azuma, Stephen Roger Holdsworth, Arthur Richard Kitching

Research output: Contribution to journalArticleResearchpeer-review

Abstract

AIM: Interactions between the co-stimulatory molecule programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, constrain T-cell responses and help maintain peripheral tolerance. Glomerulonephritis can result from a variety of antigens, both self and foreign, and from humoural and cellular effector responses. These studies aimed to define the role of PD1 and its ligands in circulating immune complex glomerulonephritis induced by immunity to a foreign antigen. METHODS: Immune complex glomerulonephritis was initiated by injecting BALB/c mice with horse spleen apoferritin intraperitoneally daily for 14 days. Inhibitory anti-mouse PD-1, anti-PD-L1 or anti-PD-L2 antibodies were administered every other day. Renal disease and immune responses were studied. RESULTS: Daily injection of horse spleen apoferritin-induced proliferative immune complex glomerulonephritis in control antibody-treated mice, but inhibiting PD-1 did not augment renal injury. Specifically, blocking PD-1 did not increase serum antigen-specific antibodies or increase glomerular immunoglobulin G deposition, the hallmark of injury in this model. Furthermore, C3 deposition was unaffected and glomerular macrophages were reduced after anti-PD-1 antibodies. However, anti-PD-1 administration did increase splenocyte proliferation and cytokine production including interferon-gamma, interleukin (IL)-4, and IL-17, but not IL-10. Neutralizing either PD-L1 or PD-L2 alone did not result in major alterations in renal injury. CONCLUSION: The endogenous PD-1/PD-L pathway does not limit acute experimental foreign antigen-induced circulating immune complex glomerulonephritis.
Original languageEnglish
Pages (from-to)892 - 898
Number of pages7
JournalNephrology
Volume20
Issue number12
DOIs
Publication statusPublished - 2015

Cite this

@article{5a1691ec55bd40d28aad6b61bfca35ec,
title = "Programmed death 1 and its ligands do not limit experimental foreign antigen-induced immune complex glomerulonephritis",
abstract = "AIM: Interactions between the co-stimulatory molecule programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, constrain T-cell responses and help maintain peripheral tolerance. Glomerulonephritis can result from a variety of antigens, both self and foreign, and from humoural and cellular effector responses. These studies aimed to define the role of PD1 and its ligands in circulating immune complex glomerulonephritis induced by immunity to a foreign antigen. METHODS: Immune complex glomerulonephritis was initiated by injecting BALB/c mice with horse spleen apoferritin intraperitoneally daily for 14 days. Inhibitory anti-mouse PD-1, anti-PD-L1 or anti-PD-L2 antibodies were administered every other day. Renal disease and immune responses were studied. RESULTS: Daily injection of horse spleen apoferritin-induced proliferative immune complex glomerulonephritis in control antibody-treated mice, but inhibiting PD-1 did not augment renal injury. Specifically, blocking PD-1 did not increase serum antigen-specific antibodies or increase glomerular immunoglobulin G deposition, the hallmark of injury in this model. Furthermore, C3 deposition was unaffected and glomerular macrophages were reduced after anti-PD-1 antibodies. However, anti-PD-1 administration did increase splenocyte proliferation and cytokine production including interferon-gamma, interleukin (IL)-4, and IL-17, but not IL-10. Neutralizing either PD-L1 or PD-L2 alone did not result in major alterations in renal injury. CONCLUSION: The endogenous PD-1/PD-L pathway does not limit acute experimental foreign antigen-induced circulating immune complex glomerulonephritis.",
author = "Joshua Ooi and Ming Li and Katerina Kourkoutzelos and Hideo Yagita and Miyuki Azuma and Holdsworth, {Stephen Roger} and Kitching, {Arthur Richard}",
year = "2015",
doi = "10.1111/nep.12532",
language = "English",
volume = "20",
pages = "892 -- 898",
journal = "Nephrology",
issn = "1320-5358",
publisher = "Wiley-Blackwell",
number = "12",

}

Programmed death 1 and its ligands do not limit experimental foreign antigen-induced immune complex glomerulonephritis. / Ooi, Joshua; Li, Ming; Kourkoutzelos, Katerina; Yagita, Hideo; Azuma, Miyuki; Holdsworth, Stephen Roger; Kitching, Arthur Richard.

In: Nephrology, Vol. 20, No. 12, 2015, p. 892 - 898.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Programmed death 1 and its ligands do not limit experimental foreign antigen-induced immune complex glomerulonephritis

AU - Ooi, Joshua

AU - Li, Ming

AU - Kourkoutzelos, Katerina

AU - Yagita, Hideo

AU - Azuma, Miyuki

AU - Holdsworth, Stephen Roger

AU - Kitching, Arthur Richard

PY - 2015

Y1 - 2015

N2 - AIM: Interactions between the co-stimulatory molecule programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, constrain T-cell responses and help maintain peripheral tolerance. Glomerulonephritis can result from a variety of antigens, both self and foreign, and from humoural and cellular effector responses. These studies aimed to define the role of PD1 and its ligands in circulating immune complex glomerulonephritis induced by immunity to a foreign antigen. METHODS: Immune complex glomerulonephritis was initiated by injecting BALB/c mice with horse spleen apoferritin intraperitoneally daily for 14 days. Inhibitory anti-mouse PD-1, anti-PD-L1 or anti-PD-L2 antibodies were administered every other day. Renal disease and immune responses were studied. RESULTS: Daily injection of horse spleen apoferritin-induced proliferative immune complex glomerulonephritis in control antibody-treated mice, but inhibiting PD-1 did not augment renal injury. Specifically, blocking PD-1 did not increase serum antigen-specific antibodies or increase glomerular immunoglobulin G deposition, the hallmark of injury in this model. Furthermore, C3 deposition was unaffected and glomerular macrophages were reduced after anti-PD-1 antibodies. However, anti-PD-1 administration did increase splenocyte proliferation and cytokine production including interferon-gamma, interleukin (IL)-4, and IL-17, but not IL-10. Neutralizing either PD-L1 or PD-L2 alone did not result in major alterations in renal injury. CONCLUSION: The endogenous PD-1/PD-L pathway does not limit acute experimental foreign antigen-induced circulating immune complex glomerulonephritis.

AB - AIM: Interactions between the co-stimulatory molecule programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, constrain T-cell responses and help maintain peripheral tolerance. Glomerulonephritis can result from a variety of antigens, both self and foreign, and from humoural and cellular effector responses. These studies aimed to define the role of PD1 and its ligands in circulating immune complex glomerulonephritis induced by immunity to a foreign antigen. METHODS: Immune complex glomerulonephritis was initiated by injecting BALB/c mice with horse spleen apoferritin intraperitoneally daily for 14 days. Inhibitory anti-mouse PD-1, anti-PD-L1 or anti-PD-L2 antibodies were administered every other day. Renal disease and immune responses were studied. RESULTS: Daily injection of horse spleen apoferritin-induced proliferative immune complex glomerulonephritis in control antibody-treated mice, but inhibiting PD-1 did not augment renal injury. Specifically, blocking PD-1 did not increase serum antigen-specific antibodies or increase glomerular immunoglobulin G deposition, the hallmark of injury in this model. Furthermore, C3 deposition was unaffected and glomerular macrophages were reduced after anti-PD-1 antibodies. However, anti-PD-1 administration did increase splenocyte proliferation and cytokine production including interferon-gamma, interleukin (IL)-4, and IL-17, but not IL-10. Neutralizing either PD-L1 or PD-L2 alone did not result in major alterations in renal injury. CONCLUSION: The endogenous PD-1/PD-L pathway does not limit acute experimental foreign antigen-induced circulating immune complex glomerulonephritis.

UR - http://onlinelibrary.wiley.com/doi/10.1111/nep.12532/epdf

U2 - 10.1111/nep.12532

DO - 10.1111/nep.12532

M3 - Article

VL - 20

SP - 892

EP - 898

JO - Nephrology

JF - Nephrology

SN - 1320-5358

IS - 12

ER -