ArticleImmunology and cell biology2011
Signaling thresholds govern heterogeneity in IL-7-receptor-mediated responses of naïve CD8(+) T cells.
Article in Immunology and cell biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 69 citations in OpenAlex.
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- Homeostatic cytokines reciprocally modulate the emergence of prenatal effector PLZF+CD4+ T cells in humans.JCI insight · 2023Article
- Shaping Heterogeneity of Naive CD8Immune network · 2023Review
- Identification of rare cell populations in autofluorescence lifetime image data.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2022Article
- The perception and response of T cells to a changing environment are based on the law of initial value.Science signaling · 2022Review
- Self-reactivity controls functional diversity of naive CD8Nature communications · 2021Article
- T cell self-reactivity during thymic development dictates the timing of positive selection.eLife · 2021Article
- Expansion of an Unusual Virtual Memory CD8Frontiers in immunology · 2021Article
- Classification of T-cell activation via autofluorescence lifetime imaging.Nature biomedical engineering · 2021Article
- Partitioning stable and unstable expression level variation in cell populations: A theoretical framework and its application to the T cell receptor.PLoS computational biology · 2020Article
- T cell receptor and cytokine signal integration in CD8Nature immunology · 2020Article
- T Cell Calcium Signaling Regulation by the Co-Receptor CD5.International journal of molecular sciences · 2018Review
- Age is not just a number: Naive T cells increase their ability to persist in the circulation over time.PLoS biology · 2018Article
- Murine Th17 cells utilize IL-2 receptor gamma chain cytokines but are resistant to cytokine withdrawal-induced apoptosis.Cancer immunology, immunotherapy : CII · 2017Article
- Adhesion- and Degranulation-Promoting Adapter Protein Promotes CD8 T Cell Differentiation and Resident Memory Formation and Function during an Acute Infection.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- The Microtubule-Associated Protein Lis1 Regulates T Lymphocyte Homeostasis and Differentiation.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- How many TCR clonotypes does a body maintain?Journal of theoretical biology · 2016Article
- Effector CD8+ T-cell Engraftment and Antitumor Immunity in Lymphodepleted Hosts Is IL7Rα Dependent.Cancer immunology research · 2015Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Variable sensitivity to T-cell-receptor (TCR)- and IL-7-receptor (IL-7R)-mediated homeostatic signals among naïve T cells has thus far been largely attributed to differences in TCR specificity. We show here that even when withdrawn from self-peptide-induced TCR stimulation, CD8(+) T cells exhibit heterogeneous responses to interleukin-7 (IL-7) that are mechanistically associated with IL-7R expression differences that correlate with relative CD5 expression. Whereas CD5(hi) and CD5(lo) T cells survive equivalently in the presence of saturating IL-7 levels in vitro, CD5(hi) T cells proliferate more robustly. Conversely, CD5(lo) T cells exhibit prolonged survival when withdrawn from homeostatic stimuli. Through quantitative experimental analysis of signaling downstream of IL-7R, we find that the enhanced IL-7 responsiveness of CD5(hi) T cells is directly related to their greater surface IL-7R expression. Further, we identify a quantitative threshold in IL-7R-mediated signaling capacity required for proliferation that lies well above an analogous threshold requirement for survival. These distinct thresholds allow subtle differences in IL-7R expression between CD5(lo) and CD5(hi) T cells to give rise to significant variations in their respective IL-7-induced proliferation, without altering survival. Heterogeneous IL-7 responsiveness is observed similarly in vivo, with CD5(hi) naïve T cells proliferating preferentially in lymphopenic mice or lymphoreplete mice administered with exogenous IL-7. However, IL-7 in lymphoreplete mice appears to be maintained at an effective level for preserving homeostasis, such that neither CD5(hi) IL-7R(hi) nor CD5(lo) IL-7R(lo) T cells proliferate or survive preferentially. Our findings indicate that IL-7R-mediated signaling not only maintains the size but also impacts the diversity of the naïve T-cell repertoire.
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