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Murine lupus in MRL/lpr mice lacking CD4 or CD8 T cells
1Amgen Research Institute, Ontario Cancer Institute, Department of Medical Biophysics, University of Toronto, Canada.
European Journal of Immunology
|September 1, 1995
Summary
Systemic lupus erythematosus in MRL/lpr mice depends on CD4+ T cells, not CD8+ T cells. CD4+ T cell deficiency reduces autoimmune disease, while CD8+ T cell deficiency does not impact survival or autoantibodies.
Area of Science:
- Immunology
- Autoimmune Diseases
- Genetics
Background:
- MRL/lpr mice exhibit systemic autoimmune disease resembling human lupus.
- Disease progression involves lymphadenopathy from CD4-8-(DN) B220+ alpha beta+ T cell accumulation.
Purpose of the Study:
- To investigate the roles of CD4+ and CD8+ T cells in MRL/lpr mouse autoimmune disease.
- To understand the contribution of specific T cell populations to disease pathogenesis.
Main Methods:
- Gene targeting in embryonic stem cells to create CD4- and CD8-deficient MRL/lpr mice.
- Analysis of survival, autoantibody levels, lymphadenopathy, splenomegaly, and T cell populations (B220+ DN T cells).
Main Results:
- CD8-/- MRL/lpr mice showed no difference in survival or autoantibodies but had reduced B220+ DN T cells.
- CD4-/- MRL/lpr mice displayed diminished autoimmune disease, reduced autoantibodies, and increased survival.
- CD4-/- MRL/lpr mice developed massive splenomegaly due to B220+ DN T cell accumulation, suggesting dissociation from disease severity.
Conclusions:
- Autoimmune disease in MRL/lpr mice is critically dependent on CD4+ T cells.
- CD8+ T cells are not essential for the development of this lupus-like disease.
- Accumulating B220+ DN T cells may follow a CD8 developmental pathway and can be dissociated from overt autoimmune pathology.