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Multiple developmental stage-specific enhancers regulate CD8 expression in developing thymocytes and in
W Ellmeier1, M J Sunshine, K Losos
1Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York 10016, USA. ellmeier@saturn.med.nyu.edu
Immunity
|November 7, 1998
Summary
The CD8 locus enhancer E8 is crucial for CD8alphaalpha homodimer expression in intestinal intraepithelial lymphocytes (IEL). Novel enhancers regulate CD8 expression in thymus-derived T cells, indicating distinct regulatory mechanisms.
Area of Science:
- Immunology
- Molecular Biology
- T cell biology
Background:
- The CD8 gene locus contains regulatory elements controlling T cell expression.
- The CD8 locus enhancer E8 (E8) directs expression in mature CD8+ T cells and intestinal intraepithelial lymphocytes (IEL).
Purpose of the Study:
- To investigate the role of E8 in regulating CD8alphaalpha homodimer expression in IEL.
- To identify additional enhancers controlling CD8 expression in T cell development and peripheral compartments.
Main Methods:
- Homologous recombination was used to delete the E8 enhancer.
- Transgenic reporter expression assays were employed to identify novel enhancers.
Main Results:
- Deletion of E8 significantly reduced CD8alphaalpha homodimer expression on IEL.
- CD8 expression on thymus-derived T cells remained normal after E8 deletion, suggesting alternative regulatory elements.
- Three novel enhancers were identified, directing expression in thymocyte subsets and mature T cells, but not in CD8alphaalpha+ IEL.
Conclusions:
- CD8alpha expression in IEL is primarily regulated by E8.
- Distinct enhancers control CD8 expression in thymus-dependent T cell lineages.
- These findings elucidate the complex transcriptional regulation of CD8 in different T cell populations.