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CD80 and CD86 costimulatory molecules regulate crescentic glomerulonephritis by different mechanisms
Dragana Odobasic1, A Richard Kitching, Peter G Tipping
1Centre for Inflammatory Diseases, Monash University, Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
Kidney International
|July 15, 2005
Summary
CD80 promotes crescentic glomerulonephritis by increasing CD4+ T cell survival, while CD86 is protective by promoting Th2 responses. The OX40/OX40-ligand pathway acts as an alternative in CD80/86-deficient mice.
Area of Science:
- Immunology
- Nephrology
Background:
- CD80 and CD86 costimulatory molecules influence Th1-mediated glomerulonephritis (GN).
- Understanding CD80/CD86 roles in anti-GBM GN is crucial.
Purpose of the Study:
- Define mechanisms of CD80 and CD86 in regulating anti-GBM GN.
- Investigate OX40-ligand's compensatory role in CD80/CD86 deficient mice.
Main Methods:
- Induced anti-GBM GN in CD80-/-, CD86-/-, and CD80/86-/- mice.
- Assessed renal injury and immune responses.
- Blocked OX40-ligand to evaluate its compensatory role.
Main Results:
- CD80 deficiency attenuated GN, reduced CD4+ T cell proliferation and increased apoptosis.
- CD86 deficiency exacerbated GN with increased IFN-gamma and decreased IL-4.
- CD80/86 deficiency resulted in GN similar to controls.
- OX40-ligand blockade worsened GN in wild-type mice but attenuated it in CD80/86-/- mice.
Conclusions:
- CD80 is pathogenic in crescentic GN by promoting CD4+ T cell survival and proliferation.
- CD86 is protective, enhancing Th2 and reducing Th1 responses.
- The OX40/OX40-ligand pathway compensates for CD80/CD86 absence in GN induction.