Suppression of lethal autoimmunity by regulatory T cells with a single TCR specificity.
The regulatory T cell (T reg cell) T cell receptor (TCR) repertoire is highly diverse and skewed toward recognition of self-antigens. TCR expression by T reg cells is continuously required for maintenance of immune tolerance and for a major part of their characteristic gene expression signature; however, it remains unknown to what degree diverse TCR-mediated interactions with cognate self-antigens are required for these processes. In this study, by experimentally switching the T reg cell TCR repertoire to a single T reg cell TCR, we demonstrate that T reg cell function and gene expression can be partially uncoupled from TCR diversity. An induced switch of the T reg cell TCR repertoire to a random repertoire also preserved, albeit to a limited degree, the ability to suppress lymphadenopathy and T helper cell type 2 activation. At the same time, these perturbations of the T reg cell TCR repertoire led to marked immune cell activation, tissue inflammation, and an ultimately severe autoimmunity, indicating the importance of diversity and specificity for optimal T reg cell function.
Duke Scholars
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Related Subject Headings
- T-Lymphocytes, Regulatory
- T-Cell Antigen Receptor Specificity
- Receptors, Antigen, T-Cell
- Mice
- Lymphocyte Activation
- Lymph Nodes
- Immunology
- Forkhead Transcription Factors
- Autoimmunity
- Animals
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- T-Lymphocytes, Regulatory
- T-Cell Antigen Receptor Specificity
- Receptors, Antigen, T-Cell
- Mice
- Lymphocyte Activation
- Lymph Nodes
- Immunology
- Forkhead Transcription Factors
- Autoimmunity
- Animals