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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 19, 2010 |
| Title |
Expression data for naïve IL-2 and IL-12 primed Pmel-1 CD8+ T-cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The expansion, trafficking and functional effectiveness of adoptively transferred CD8+ T-cells play a critical role in mediating effective anti-tumor immunity. However, the mechanisms which program the highly proliferative and functional state of CD8+ T-cells are not completely understood. We hypothesized that IL-12, a cytokine commonly induced by TLR activation, could enhance T-cell priming by altering responsiveness to antigen and cytokines. Priming of tumor specific CD8+ T-cells in the presence of IL-12 induced the acquisition of a 'polyfunctional' effector response and increased the generation of memory cells. Moreover, IL-12 priming also promoted high levels of the IL-2 receptor alpha-chain (CD25) and robust IL-2 mediated activation of STAT5. This sensitivity to IL-2 translated into enhanced in vivo proliferation of adoptively transferred CD8+ T-cells. Furthermore, real-time, in vivo imaging of T-cell trafficking confirmed the ability of IL-12 priming to drive in vivo proliferation. IL-12 priming enhanced the anti-tumor function of adoptively transferred cells by reducing established subcutaneous tumor burden, and significantly increasing survival in an established intracranial tumor model. Finally, IL-12 priming of human PBMCs generates tumor specific T-cells phenotypically and functionally similar to IL-12 primed Pmel-1 T-cells. These results highlight IL-12 as an important mediator of CD8+ T-cell effector function and anti-tumor immunity.
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| Overall design |
We primed Pmel-1 TCR transgenic CD8+ T-cells with cognate antigen and either IL-2 or IL-12 and compared their gene expression profiles. This was used to identify pathways or genes necessary for anti-tumor activity in vivo.
RNA was isolated from Pmel-1 T-cells primed with antigen and cytokine for 6 days and hybridized to Affymetrix arrays.
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| Contributor(s) |
Prins R, Lisiero D |
| Citation(s) |
21430221 |
| Submission date |
Jun 18, 2010 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Robert M Prins |
| Organization name |
UCLA
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| Department |
Neurosurgery
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| Street address |
1506 Gonda
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA128523 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE22443_RAW.tar |
25.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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