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Open Access Green as soon as Postprint is submitted to ZB.
IL-7 abrogates suppressive activity of human CD4+CD25+FOXP3+ regulatory T cells and allows expansion of alloreactive and autoreactive T cells.
J. Immunol. 189, 5649-5658 (2012)
CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) control the activation and expansion of alloreactive and autoreactive T cell clones. Because uncontrolled activation and expansion of autoreactive T cells occur in an IL-7-rich environment, we explored the possibility that IL-7 may affect the function of Treg. We show that the functional high-affinity IL-7R is expressed on both naive and memory Tregs, and exposure to IL-7 results in STAT-5 phosphorylation. Naive, but not memory, Tregs proliferated greatly and acquired a memory phenotype in the setting of a suppression assay when IL-7 was present. Importantly, the presence of IL-7 abrogated the capacity of Tregs to suppress proliferation of conventional T cells in response to TCR activators, including alloantigens and autoantigens. Removal of IL-7 restored the suppressive function of Tregs. Preblocking of the IL-7R on the Tregs also restored suppressor function, indicating that IL-7 directly affected Treg function. Thus, prolonged periods of homeostatic expansion can temporarily release natural regulatory brakes on T cells, thereby providing an additional mechanism for activating and expanding alloreactive and autoreactive T cells.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
0022-1767
e-ISSN
1550-6606
Journal
Journal of Immunology
Quellenangaben
Volume: 189,
Issue: 12,
Pages: 5649-5658
Publisher
American Association of Immunologists
Reviewing status
Peer reviewed
Institute(s)
Institute of Pancreatic Islet Research (IPI)