Related Experiment Video
Updated: May 8, 2026
Orthotopic Rat Kidney Transplantation: A Novel and Simplified Surgical Approach
Published on: May 7, 2019
Blockade of OX40/OX40 ligand to decrease cytokine messenger RNA expression in acute renal allograft rejection in
1Department of Transplantation Surgery, Central Laboratory, Tianjin First Central Hospital, Key Lab for Critical Care Medicine of the Ministry of Health, Tianjin, China.
Aim:
The aim of this study was to investigate cytokine messenger RNA (mRNA) expression by peripheral blood mononuclear cells (PBMCs) from renal recipients experiencing acute rejection by blocking OX40-OX40L interactions with recombinant human OX40-Fc fusion protein (rhOX40Fc) in vitro.
Methods:
PBMCs were isolated from 20 recipients experiencing acute rejection episodes (rejection group) and 20 recipients with stable graft function (stable group). Levels of Th1 (interferon [IFN]-γ) and Th2 (interleukin [IL]-4) mRNA expressions by PBMCs were measured using real-time reverse transcriptase-polymerase chain reactions.
Results:
IFN-γ mRNA expression levels were significantly higher in the rejection than the stable group (P < .05). Levels of IL-4 mRNA expression were not significantly different. Among the rejection group, rhOX40Fc reduced significantly the expression of IFN-γ and IL-4 mRNA by anti-CD3-monoclonal antibody stimulated PBMCs (P < .05, and P < .01, respectively).
Conclusions:
Blocking of the interaction between OX40 and OX40L in vitro inhibited production of Thl and Th2 type cytokines.
Insights
Blocking OX40-OX40L interactions with rhOX40Fc in vitro significantly reduced Th1 and Th2 cytokine mRNA in renal transplant recipients with acute rejection. This suggests a therapeutic target for preventing transplant rejection.
Area of Science:
- Immunology
- Transplantation Biology
- Molecular Medicine
Background:
- Acute rejection remains a significant challenge in renal transplantation.
- Cytokine production by peripheral blood mononuclear cells (PBMCs) plays a crucial role in transplant rejection.
- The OX40-OX40L pathway is implicated in T-cell activation and immune responses.
Purpose of the Study:
- To investigate the effect of blocking OX40-OX40L interactions on cytokine mRNA expression in renal transplant recipients with acute rejection.
- To evaluate the potential of recombinant human OX40-Fc fusion protein (rhOX40Fc) as a therapeutic agent in vitro.
Main Methods:
- PBMCs were isolated from renal transplant recipients experiencing acute rejection (rejection group) and those with stable graft function (stable group).
- Messenger RNA (mRNA) expression levels of Th1 (interferon-gamma [IFN-γ]) and Th2 (interleukin-4 [IL-4]) cytokines were quantified using real-time reverse transcriptase-polymerase chain reactions.
- The impact of rhOX40Fc on cytokine mRNA expression was assessed in anti-CD3-monoclonal antibody stimulated PBMCs from the rejection group.
Main Results:
- IFN-γ mRNA expression was significantly higher in the rejection group compared to the stable group (P < .05).
- IL-4 mRNA expression levels did not differ significantly between the groups.
- In the rejection group, rhOX40Fc treatment significantly reduced both IFN-γ and IL-4 mRNA expression (P < .05 and P < .01, respectively).
Conclusions:
- In vitro blockade of OX40-OX40L interaction effectively inhibited the production of Th1 and Th2 type cytokines.
- These findings highlight the potential of targeting the OX40-OX40L pathway to modulate immune responses in renal transplant rejection.
