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A self-reactive T cell population that is not subject to negative selection
E A Robey1, F Ramsdell, J W Gordon
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032.
International Immunology
|September 1, 1992
Summary
T cells lacking normal CD8 levels in male mice escape deletion and exhibit unique phenotypes. Introducing a CD8 transgene influences T cell populations, suggesting CD4-CD8- T cells may evade deletion.
Area of Science:
- Immunology
- T cell biology
- Transgenic mouse models
Background:
- T cells expressing a specific T cell receptor (TCR) for male antigen (HY) typically require CD8 for function.
- In male mice with an anti-HY TCR transgene, T cells with suboptimal CD8 expression escape thymic deletion.
Purpose of the Study:
- To investigate the impact of co-expressing an anti-HY TCR transgene and a constitutive CD8.1 transgene on T cell populations in male mice.
- To determine the fate of T cells with varying CD8 expression levels in the presence of both transgenes.
Main Methods:
- Generation of 'double transgenic' male mice expressing both anti-HY TCR and CD8.1 transgenes.
- Flow cytometry analysis of peripheral T cell populations (CD4, CD8, TCR expression).
- In vitro proliferation assays to assess T cell reactivity to male antigen.
Main Results:
- Double transgenic male mice possess peripheral T cells expressing the anti-HY TCR and normal CD8 levels.
- These T cells proliferate in response to male antigen in vitro.
- The CD8.1 transgene appears to induce deletion of CD8.2low T cells but not CD8.2- T cells.
Conclusions:
- Constitutive CD8 expression influences T cell selection in TCR transgenic mice.
- The CD8.1 transgene leads to the deletion of CD8.2low T cells, but not CD8.2- T cells.
- TCR+CD4-CD8- T cells in TCR transgenic mice may not undergo deletion, suggesting a distinct developmental pathway.