Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 214, Issue 3, Pages 609-622Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20161318
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Funding
- National Institutes of Health (NIH) Medical Scientist Training Program grant [T32GM07739]
- Frank Lappin Horsfall Jr. Student Fellowship
- NIH grant [R37AI034206]
- Ludwig Center at Memorial Sloan-Kettering Cancer Center
- Hilton-Ludwig Cancer Prevention Initiative of the Conrad N. Hilton Foundation
- Ludwig Cancer Research
- NIH/National Cancer Institute Cancer Center Support [P30 CA008748]
- Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH
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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.
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