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T cell receptor revision does not solely target recent thymic emigrants
Cristine J Cooper1, Mark T Orr, Catherine J McMahan
1Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|June 21, 2003
Summary
Peripheral T cells can undergo T-cell receptor (TCR) revision, a tolerance pathway involving recombinase-activating gene (RAG) reinduction. This process rescues T cells by allowing them to express a new TCR, even in mature, peripheral cells.
Area of Science:
- Immunology
- T-cell biology
- Peripheral tolerance mechanisms
Background:
- CD4(+)Vbeta5(+) T cells encountering superantigens initiate tolerance pathways: deletion or TCR revision.
- TCR revision allows T-cell rescue by expressing an alternate TCR, requiring TCR beta-chain gene rearrangement and RAG expression in peripheral T cells.
Purpose of the Study:
- To investigate the hypothesis that TCR revision is limited to recent thymic emigrants with maintained RAG expression.
- To determine if RAG gene reinduction in peripheral T cells triggers TCR revision.
Main Methods:
- Utilized RAG2 promoter-driven green fluorescent protein reporter mice to track RAG expression in T cells.
- Employed thymectomized Vbeta5 transgenic RAG reporter mice to assess TCR revision in peripheral T cells post-thymectomy.
Main Results:
- In vitro stimulation induced RAG reporter expression in mature, noncycling, peripheral CD4(+) T cells.
- TCR revision was observed in peripheral T cells up to 2 months after thymectomy, indicating RAG reinduction triggers the process.
- Approximately 3% of CD4(+)Vbeta5(+) T cells underwent TCR revision within 4-5 days in thymectomized mice.
Conclusions:
- TCR revision is not restricted to recent thymic emigrants and can be triggered by RAG gene reinduction in mature peripheral T cells.
- This study demonstrates TCR revision occurs in unmanipulated mice, highlighting its relevance as a peripheral tolerance mechanism.