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Altered immune responses in apolipoprotein E-deficient mice.
D T Laskowitz1, D M Lee, D Schmechel
1Department of Medicine (Neurology), Duke University Medical Center, Durham, NC 27710, USA.
Journal of Lipid Research
|April 1, 2000
Summary
Apolipoprotein E (apoE) influences immune responses. ApoE deficiency in mice altered antibody production and delayed hypersensitivity, suggesting apoE regulates both humoral and cell-mediated immunity.
Area of Science:
- Immunology
- Lipid Metabolism
- Protein Function
Background:
- Apolipoprotein E (apoE) is a protein involved in cholesterol transport.
- Emerging evidence suggests apoE possesses in vitro immunomodulatory properties.
- Previous studies indicated apoE-deficient mice exhibit altered immune responses and increased susceptibility to endotoxemia.
Purpose of the Study:
- To investigate the mechanism by which apoE modulates immune responses.
- To assess the role of human apoE isoforms (E3 and E4) in T cell proliferation.
- To analyze the immune responses in apoE-deficient mice.
Main Methods:
- Assays of human T cell proliferation, including responses to phytohemagglutinin (PHA), anti-CD3, and tetanus toxoid.
- Analysis of lymphocyte populations in thymic, splenic, and bone marrow of apoE-deficient mice.
- Assessment of splenocyte proliferation and delayed type hypersensitivity responses in apoE-deficient mice post-immunization with tetanus toxoid.
Main Results:
- Both apoE E3 and E4 isoforms suppressed human lymphocyte proliferation in vitro.
- ApoE-deficient mice showed no quantitative differences in lymphocyte populations or inherent T cell defects.
- ApoE-deficient mice exhibited elevated antigen-specific IgM levels and impaired delayed type hypersensitivity responses.
Conclusions:
- ApoE plays a significant role in regulating both humoral and cell-mediated immunity.
- These findings highlight the interplay between lipid metabolism and immune system regulation.
- ApoE's immunomodulatory effects are biologically relevant in vivo.