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| Status |
Public on Jul 02, 2021 |
| Title |
Fever supports CD8+ effector T cell responses by promoting mitochondrial translation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Fever can provide a survival advantage during infection. Metabolic processes are sensitive to environmental conditions, but the effect of fever on T cell metabolism is not well characterized. We show that in activated CD8+ T cells, exposure to febrile temperature (39°C) augmented metabolic activity and T cell effector functions, despite having a limited effect on proliferation or activation marker expression. Transcriptional profiling revealed an upregulation of mitochondrial pathways, which was consistent with increased mitochondrial metabolism and mass observed in T cells exposed to 39°C. Through in vitro and in vivo models we determined that mitochondrial translation is integral to the enhanced metabolic activity and function of CD8+ T cells exposed to febrile temperature. Transiently exposing donor lymphocytes to 39°C prior to infusion in a myeloid leukemia (ML) mouse model conferred enhanced therapeutic efficacy, raising the possibility that exposure of T cells to febrile temperatures could have clinical potential.
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| Overall design |
Naive CD8+ T cells were isolated from spleen and lymph nodes from 6-12 week old micel. Isolated T cells (1x10^6/ml) were activated using plate bound αCD3 (5 μg/ml) and soluble αCD28 (0.5 μg/ml) in T cell media (TCM; 1640 RPMI with 10% fatal calf serum, 4mM L-glutamine, 1% penicillin/streptomycin, 55μM beta-mercaptoethanol) supplemented with 100 U/ml hrIL-2 (Peprotech). Cells were cultured a 37°C or 39°C as indicated in humidified incubators with 5% CO2 and atmospheric oxygen for 24 or 48 hours following activation. RNA was extracted from 3 independent biological replicates in each treatment and then sequenced.
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| Contributor(s) |
O’Sullivan D, Stanczak M, Villa M, Uhl FM, Corrado M, Klein Geltink RI, Sanin DE, Apostolova P, Rana N, Edwards-Hicks J, Grzes K, Kabat A, Kyle R, Fabri M, Curtis JD, Buck MD, Patterson AE, Field CS, Baixauli F, Puleston DJ, Pearce EJ, Zeiser R, Pearce EL |
| Citation(s) |
34161266, 36732424 |
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| Submission date |
Mar 31, 2021 |
| Last update date |
Mar 13, 2024 |
| Contact name |
Immunometabolism Department |
| E-mail(s) |
jcurti29@jhmi.edu
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| Organization name |
Johns Hopkins University
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| Department |
Immunometabolism
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| Street address |
1650 Orleans Street
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21287 |
| Country |
USA |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA718850 |
| SRA |
SRP312911 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE171245_RAW.tar |
2.2 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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