CD8+ T cell self-tolerance permits responsiveness but limits tissue damage
- University of Minnesota Medical School, United States
- NIH, United States
- Agentus Therapeutics, United States
- Grand Valley State University, United States
Abstract
Self-specific CD8+ T cells can escape clonal deletion, but the properties and capabilities of such cells in a physiological setting are unclear. We characterized polyclonal CD8+ T cells specific for the melanocyte antigen tyrosinase-related protein 2 (Trp2) in mice expressing or lacking this enzyme (due to deficiency in Dct, which encodes Trp2). Phenotypic and gene expression profiles of pre-immune Trp2/Kb-specific cells were similar; the size of this population was only slightly reduced in wild-type (WT) compared to Dct-deficient (Dct-/-) mice. Despite comparable initial responses to Trp2 immunization, WT Trp2/Kb-specific cells showed blunted expansion and less readily differentiated into a CD25+ proliferative population. Functional self-tolerance clearly emerged when assessing immunopathology: adoptively transferred WT Trp2/Kb-specific cells mediated vitiligo much less efficiently. Hence, CD8+ T cell self-specificity is poorly predicted by precursor frequency, phenotype or even initial responsiveness, while deficient activation-induced CD25 expression and other gene expression characteristics may help to identify functionally tolerant cells.
Data availability
NextGen sequencing data has being deposited at GEO: Code GSE171221.
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Non-deletional CD8+ T cell self-tolerance permits responsiveness but limits tissue damageNCBI Gene Expression Omnibus, GSE171221.
Article and author information
Author details
Emily N Truckenbrod
Funding
National Institute of Allergy and Infectious Diseases (R01AI140631)
- Stephen C Jameson
National Institute of Allergy and Infectious Diseases (P01AI035296)
- Stephen C Jameson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the NIH Guide for the Care and Use of Laboratory Animals and handled according to protocols approved but the University of Minnesota IACUC (#1709-35136A and #2007-38243A).
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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CD8+ T cell self-tolerance permits responsiveness but limits tissue damage
eLife 10:e65615.
https://doi.org/10.7554/eLife.65615
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