Cd8+ t cell self-tolerance permits responsiveness but limits tissue damage

Emily N Truckenbrod, Kristina S Burrack, Todd P Knutson, Henrique Borges da Silva, Katharine E Block, Stephen D O'Flanagan, Katie R Stagliano, Arthur A Hurwitz, Ross B Fulton, Kristin R Renkema, Stephen C Jameson

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article numbere65615
JournaleLife
Volume10
DOIs
StatePublished - Apr 30 2021

Bibliographical note

Funding Information:
This work was supported by NIH grants P01 AI035296 (SCJ), R01 AI140631 (SCJ), and T32 OD010993 (ENT).

Publisher Copyright:
© 2021, eLife Sciences Publications Ltd. All rights reserved.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

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