Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 38, Issue 1, Pages 30-39Publisher
WILEY
DOI: 10.1002/eji.200737852
Keywords
CD4 T cells; cellular activation; cytokines; gene expression; signal transduction
Categories
Funding
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U19AI057266] Funding Source: NIH RePORTER
- NIAID NIH HHS [U19AI057266-01] Funding Source: Medline
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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.
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