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| Status |
Public on Apr 30, 2021 |
| Title |
Non-deletional CD8+ T cell self-tolerance permits responsiveness but limits tissue damage |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Self-specific CD8+ T cells often 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 that express or lack this enzyme due to deficiency in Dct, which encodes Trp2. The size, phenotype, and gene expression profile of the pre-immune Trp2/Kb-specific pool were similar in wild-type (WT) and Dct-deficient (Dct-/-) mice. Despite comparable initial responses to Trp2 immunization, WT Trp2/Kb-specific cells showed blunted expansion, and scRNAseq revealed WT cells 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.
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| Overall design |
Comparison of tolerant (WT) versus non-tolerant (KO or Dct-/-) CD8+ Trp2-specific cells. Number, phenotype, expansion, and functionality were compared. This analysis included gene expression comparisons between Trp2-specific cells from WT vs. KO/Dct-/- naive mice (bulk RNAseq in pre-immune mice) and mice treated with TriVax 3 or 7 days prior (single cell [sc] RNAseq).
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| Contributor(s) |
Truckenbrod EN, Burrack KS, Knutson TP, Borges da Silva H, Block KE, Stagliano KR, Hurwitz AA, Fulton RB, Renkema KR, Jameson SC |
| Citation(s) |
33929324 |
| Submission date |
Mar 31, 2021 |
| Last update date |
Aug 02, 2021 |
| Contact name |
Todd P Knutson |
| E-mail(s) |
knut0297@umn.edu
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| Phone |
612-626-8911
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| Organization name |
University of Minnesota
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| Department |
Minnesota Supercomputing Institute
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| Street address |
117 Pleasant St SE
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| City |
Minneapolis |
| State/province |
MN |
| ZIP/Postal code |
55455 |
| Country |
USA |
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| Platforms (2) |
| GPL21626 |
NextSeq 550 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (10)
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| GSM5220996 |
antigen-specific CD8+ T cells Trp2 (Dct) wild-type bulk cells replicate 1 |
| GSM5220997 |
antigen-specific CD8+ T cells Trp2 (Dct) wild-type bulk cells replicate 2 |
| GSM5220998 |
antigen-specific CD8+ T cells Trp2 (Dct) wild-type bulk cells replicate 3 |
| GSM5220999 |
antigen-specific CD8+ T cells Trp2 (Dct) knockout bulk cells replicate 1 |
| GSM5221000 |
antigen-specific CD8+ T cells Trp2 (Dct) knockout bulk cells replicate 2 |
| GSM5221001 |
antigen-specific CD8+ T cells Trp2 (Dct) knockout bulk cells replicate 3 |
| GSM5221002 |
antigen-specific CD8+ T cells Trp2 (Dct) wild-type single cells_day3 |
| GSM5221003 |
antigen-specific CD8+ T cells Trp2 (Dct) knockout single cells_day3 |
| GSM5221004 |
antigen-specific CD8+ T cells Trp2 (Dct) wild-type single cells_day7 |
| GSM5221005 |
antigen-specific CD8+ T cells Trp2 (Dct) knockout single cells_day7 |
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| Relations |
| BioProject |
PRJNA718819 |
| SRA |
SRP312890 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE171221_experiment_1_bulk_rnaseq_norm_counts.txt.gz |
756.9 Kb |
(ftp)(http) |
TXT |
| GSE171221_experiment_1_bulk_rnaseq_raw_counts.txt.gz |
444.7 Kb |
(ftp)(http) |
TXT |
| GSE171221_experiment_2_singlecell_rnaseq_day3_norm_counts.txt.gz |
304.4 Mb |
(ftp)(http) |
TXT |
| GSE171221_experiment_2_singlecell_rnaseq_day3_raw_counts.txt.gz |
34.0 Mb |
(ftp)(http) |
TXT |
| GSE171221_experiment_2_singlecell_rnaseq_day7_norm_counts.txt.gz |
135.3 Mb |
(ftp)(http) |
TXT |
| GSE171221_experiment_2_singlecell_rnaseq_day7_raw_counts.txt.gz |
15.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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