Mouse memory T cell precursors express IL-7 receptor-a (IL-7R), proliferate with homeostatic cytokines and undergo secondary expansions with antigen. Here, we analyzed how the strength of antigenic stimulation regulates IL-7R expression, cytokine responsiveness and expansion potential of DC-primed human CD4(+) T cells. IL-7R expression on proliferating T cells was highest at intermediate strength of stimulation, and purified CCR7(+)IL-7R(hi) and CCR7(-)IL-7R(lo) subsets had characteristics of memory and effector cells, respectively. However, CCR7(+)IL-7R(hi) cells generated under different priming conditions had strikingly different properties. Thus, increasing strength of stimulation promoted IL-7 responsiveness that correlated with reduced phosphatase and tensin homologue deleted on chromosome 10 (PTEN) expression and enhanced s6 kinase activation, suggesting a tunable IL-7R coupling to P13 kinase-dependent signaling pathways. Furthermore, functional and gene expression analysis revealed that intermediate-stimulated CCR7(+)IL-7R(hi) cells were similar to non-polarized central memory cells with high expansion potential. Conversely, high-stimulated CCR7(+) IL-7R(hi) cells shared characteristics with circulating pre-Th 1 cells and differentiated spontaneously to Th1 effector cells. These results show that the strength of stimulation determines properties of activated IL-7R(hi) T cells, and suggest that memory T cell subsets could be derived from CCR7+ precursors that received different strengths of stimulation.

The strength of T cell stimulation determines IL-7 responsiveness, secondary expansion, and lineage commitment of primed human CD4(+)IL-7R(hi) T cells / L. Lozza, L. Rivino, G. Guarda, D. Jarrossay, A. Rinadi, F. Bertoni, F. Sallusto, A. Lanzavecchia, J. Geginat. - In: EUROPEAN JOURNAL OF IMMUNOLOGY. - ISSN 0014-2980. - 38:1(2008), pp. 30-39. [10.1002/eji.2007378521]

The strength of T cell stimulation determines IL-7 responsiveness, secondary expansion, and lineage commitment of primed human CD4(+)IL-7R(hi) T cells

J. Geginat
2008

Abstract

Mouse memory T cell precursors express IL-7 receptor-a (IL-7R), proliferate with homeostatic cytokines and undergo secondary expansions with antigen. Here, we analyzed how the strength of antigenic stimulation regulates IL-7R expression, cytokine responsiveness and expansion potential of DC-primed human CD4(+) T cells. IL-7R expression on proliferating T cells was highest at intermediate strength of stimulation, and purified CCR7(+)IL-7R(hi) and CCR7(-)IL-7R(lo) subsets had characteristics of memory and effector cells, respectively. However, CCR7(+)IL-7R(hi) cells generated under different priming conditions had strikingly different properties. Thus, increasing strength of stimulation promoted IL-7 responsiveness that correlated with reduced phosphatase and tensin homologue deleted on chromosome 10 (PTEN) expression and enhanced s6 kinase activation, suggesting a tunable IL-7R coupling to P13 kinase-dependent signaling pathways. Furthermore, functional and gene expression analysis revealed that intermediate-stimulated CCR7(+)IL-7R(hi) cells were similar to non-polarized central memory cells with high expansion potential. Conversely, high-stimulated CCR7(+) IL-7R(hi) cells shared characteristics with circulating pre-Th 1 cells and differentiated spontaneously to Th1 effector cells. These results show that the strength of stimulation determines properties of activated IL-7R(hi) T cells, and suggest that memory T cell subsets could be derived from CCR7+ precursors that received different strengths of stimulation.
CD4 T cells; cellular activation; cytokines; gene expression; signal transduction
Settore MED/04 - Patologia Generale
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/730445
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