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Strength of T cell stimulation

ABSTRACT: 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE6566 | GEO | 2007/12/18

SECONDARY ACCESSION(S): PRJNA98739

REPOSITORIES: GEO

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Project 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.

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