E-GEOD-6566 - Transcription profiling of human T cells to determine the strength of T cell stimulation

Status
Submitted on 19 December 2006, released on 14 June 2008, last updated on 27 March 2012
Organism
Homo sapiens
Samples (4)
Array (1)
Protocols (7)
Description
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. Experiment Overall Design: two samples treated with weaker dendritic stimulus, two samples treated with stonger dendritic stimulus.
Experiment types
transcription profiling by array, unknown experiment type
Contact
Citation
The strength of T cell stimulation determines IL-7 responsiveness, secondary expansion, and lineage commitment of primed human CD4+IL-7Rhi T cells. Laura Lozza, Laura Rivino, Greta Guarda, David Jarrossay, Andrea Rinaldi, Francesco Bertoni, Federica Sallusto, Antonio Lanzavecchia, Jens Geginat. Eur J Immunol 38(1):30-9 (2008)
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-6566.idf.txt
Sample and data relationshipE-GEOD-6566.sdrf.txt
Raw data (1)E-GEOD-6566.raw.1.zip
Processed data (1)E-GEOD-6566.processed.1.zip
Array designA-AFFY-44.adf.txt
R ExpressionSetE-GEOD-6566.eSet.r
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