The strength of T cell stimulation determines IL-7 responsiveness, secondary expansion, and lineage commitment of primed human CD4+IL-7Rhi T cells.

Détails

ID Serval
serval:BIB_817007B2B17D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The strength of T cell stimulation determines IL-7 responsiveness, secondary expansion, and lineage commitment of primed human CD4+IL-7Rhi T cells.
Périodique
European Journal of Immunology
Auteur(s)
Lozza L., Rivino L., Guarda G., Jarrossay D., Rinaldi A., Bertoni F., Sallusto F., Lanzavecchia A., Geginat J.
ISSN
0014-2980 (Print)
ISSN-L
0014-2980
Statut éditorial
Publié
Date de publication
2008
Volume
38
Numéro
1
Pages
30-39
Langue
anglais
Résumé
Mouse memory T cell precursors express IL-7 receptor-alpha (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 PI3 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-Th1 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.
Mots-clé
CD4-Positive T-Lymphocytes/cytology, CD4-Positive T-Lymphocytes/immunology, Cell Lineage, Cells, Cultured, Cytokines, Flow Cytometry, Gene Expression, Gene Expression Profiling, Humans, Immunologic Memory, Interleukin-7/immunology, Lymphocyte Activation/immunology, Oligonucleotide Array Sequence Analysis, Receptors, CCR7/immunology, Receptors, Interleukin-7/biosynthesis, Receptors, Interleukin-7/immunology, T-Lymphocyte Subsets/cytology, T-Lymphocyte Subsets/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/03/2012 16:39
Dernière modification de la notice
08/05/2019 21:09
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