IL-7 abrogates suppressive activity of human CD4+ CD25 + FOXP3+ regulatory T cells and allows expansion of alloreactive and autoreactive T cells

Anne Kristin Heninger, Anke Theil, Carmen Wilhelm, Cathleen Petzold, Nicole Huebel, Karsten Kretschmer, Ezio Bonifacio, Paolo Monti

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)5649-5658
Number of pages10
JournalJournal of Immunology
Volume189
Issue number12
DOIs
Publication statusPublished - Dec 15 2012

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Interleukin-7
Regulatory T-Lymphocytes
Human Activities
T-Lymphocytes
Isoantigens
Autoantigens
Clone Cells
Phosphorylation
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

IL-7 abrogates suppressive activity of human CD4+ CD25 + FOXP3+ regulatory T cells and allows expansion of alloreactive and autoreactive T cells. / Heninger, Anne Kristin; Theil, Anke; Wilhelm, Carmen; Petzold, Cathleen; Huebel, Nicole; Kretschmer, Karsten; Bonifacio, Ezio; Monti, Paolo.

In: Journal of Immunology, Vol. 189, No. 12, 15.12.2012, p. 5649-5658.

Research output: Contribution to journalArticle

Heninger, AK, Theil, A, Wilhelm, C, Petzold, C, Huebel, N, Kretschmer, K, Bonifacio, E & Monti, P 2012, 'IL-7 abrogates suppressive activity of human CD4+ CD25 + FOXP3+ regulatory T cells and allows expansion of alloreactive and autoreactive T cells', Journal of Immunology, vol. 189, no. 12, pp. 5649-5658. https://doi.org/10.4049/jimmunol.1201286
Heninger, Anne Kristin ; Theil, Anke ; Wilhelm, Carmen ; Petzold, Cathleen ; Huebel, Nicole ; Kretschmer, Karsten ; Bonifacio, Ezio ; Monti, Paolo. / IL-7 abrogates suppressive activity of human CD4+ CD25 + FOXP3+ regulatory T cells and allows expansion of alloreactive and autoreactive T cells. In: Journal of Immunology. 2012 ; Vol. 189, No. 12. pp. 5649-5658.
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