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Down-regulation of CD28 expression by TNF-alpha.
E Bryl1, A N Vallejo, C M Weyand
1Department of Medicine and Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|September 7, 2001
Summary
Tumor necrosis factor-alpha (TNF-alpha) reduces CD28 expression on T cells, leading to the emergence of CD4(+)CD28(null) T cells. This mechanism may explain their increased frequency in aging and chronic inflammatory conditions like rheumatoid arthritis.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Aging and chronic inflammatory diseases like rheumatoid arthritis are linked to increased CD4(+)CD28(null) T cells.
- Elevated levels of tumor necrosis factor-alpha (TNF-alpha) are observed in these conditions.
Purpose of the Study:
- To investigate the effect of TNF-alpha on CD28 expression and T cell populations.
- To elucidate the molecular mechanisms by which TNF-alpha influences CD28 gene transcription.
Main Methods:
- Incubation of T cell lines, clones, and Jurkat cells with TNF-alpha.
- Reporter gene assays to assess CD28 promoter activity.
- DNA-protein binding assays and in vitro transcription assays.
Main Results:
- TNF-alpha reduced cell surface CD28 expression, which was reversible.
- Continuous TNF-alpha exposure led to the emergence of CD28(null) T cells.
- TNF-alpha inhibited CD28 promoter activity by reducing DNA-protein complex formation and impairing transcription initiation.
Conclusions:
- TNF-alpha directly suppresses CD28 gene transcription.
- Increased TNF-alpha production may facilitate the in vivo development of CD4(+)CD28(null) T cells in aging and inflammatory states.