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| Status |
Public on Dec 18, 2007 |
| Title |
Strength of T cell stimulation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The strength of T cell stimulation determines IL-7 responsiveness, recall potential and lineage commitment of primed human CD4+IL-7Rhi T cells
We analyzed how the strength of antigenic stimulation - as determined by dendritic cell (DC) number, DC maturation state and antigen concentration - controls in human CD4+ T cells IL-7R? expression and responsiveness to IL-7, IL-15 and antigen. We found that T cells primed by different strengths of stimulation expressed IL-7R? in different proportions and preferentially on cells that maintained expression of the central memory marker CCR7. However, while CCR7+IL-7Rhi cells generated at high strength of stimulation proliferated vigorously in response to IL-7 or IL-15, CCR7+IL-7Rhi cells generated at low strength of stimulation responded poorly. High cytokine responsiveness was associated with reduced PTEN expression and enhanced s6-kinase activation, consistent with efficient receptor coupling to downstream signalling pathways. Interestingly, while intermediate-stimulated CCR7+IL-7Rhi cells were non-polarized, self-renewed with IL-7 and expanded with antigen, high-stimulated cells generated Th1 effector cells with cytokines but showed impaired IL-2 production and survival with antigen. Gene expression analysis suggested that high-stimulated cells represented pre-Th1 cells with low recall potential and high metabolic state. Taken together these results demonstrate that IL-7 receptor expression and coupling are instructed in T cells by the strength of stimulation and suggest that memory subsets may derive from CCR7+IL-7Rhi precursors that received different strengths of stimulation.
Keywords: comparison
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| Overall design |
two samples treated with weaker dendritic stimulus, two samples treated with stonger dendritic stimulus.
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| Contributor(s) |
Lozza L, Rivino L, Guarda G, Jarrossay D, Rinaldi A, Bertoni F, Sallusto F, Lanzavecchia A, Geginat J |
| Citation(s) |
18081042 |
| Submission date |
Dec 19, 2006 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Francesco Bertoni |
| E-mail(s) |
francesco.bertoni@ior.usi.ch
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| Phone |
+41 91 820 0367
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| Organization name |
IOR
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| Department |
Lymphoma & Genomics Research Program
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| Street address |
Via V. Vela 6
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| City |
Bellinzona |
| State/province |
Ticino |
| ZIP/Postal code |
6500 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA98739 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE6566_RAW.tar |
14.6 Mb |
(http)(custom) |
TAR (of CEL) |
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