IL-7 mediated homeostatic expansion of human CD4+CD25+FOXP3+ regulatory T cells after depletion with anti-CD25 monoclonal antibody

Debora Vignali, Clara-Marie Gürth, Silvia Pellegrini, Valeria Sordi, Federico Sizzano, Lorenzo Piemonti, Paolo Monti

Research output: Contribution to journalArticle

Abstract

The maintenance or expansion of regulatory T (Treg) cells has a fundamental role in the achievement of immunological tolerance after transplantation. Here we aimed to determine mechanisms of human Treg cell depletion and reconstitution after anti-CD25monoclonal antibody (mAb) treatment.Methods. Seventeen patients with type 1 diabetes who received pancreatic islet transplantation and anti-CD25 mAb as induction therapy were studied. Results.We observed an almost complete depletion of Treg cells after injection of anti-CD25 mAb. The kinetic of Treg cell depletion did not parallel the disappearance of CD25+ Tcells as CD25 is also rapidly downregulated and internalized. Regulatory Tcell reconstitution is completed within 6 months posttransplantation and appeared to be driven by IL-7-mediated homeostatic Tcell proliferation. Anti-CD25 mAb treatment sensitizes Treg cell to the biological effect of IL-7, possibly rendering more common γc-chain available to interact with CD127. Homeostatic Treg cell proliferation is resistant to the inhibitory effect of rapamycin and FK506 but can be blocked by the presence of mycophenolate mofetil. Conclusions. Our data suggest that a compensatory mechanism of IL-7-mediated homeostatic proliferation can restore the inhibitory network of Treg cell after anti-CD25 induction therapy in islet allotransplantation.
Original languageEnglish
Pages (from-to)1853 - 1861
Number of pages9
JournalTransplantation
Volume100
Issue number9
DOIs
Publication statusPublished - Aug 23 2016

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Interleukin-7
Regulatory T-Lymphocytes
Monoclonal Antibodies
Mycophenolic Acid
Transplantation Tolerance
Islets of Langerhans Transplantation
Tacrolimus
Sirolimus
Therapeutics
Type 1 Diabetes Mellitus
Anti-Idiotypic Antibodies
Down-Regulation
Maintenance
Cell Proliferation
Injections

ASJC Scopus subject areas

  • Transplantation

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IL-7 mediated homeostatic expansion of human CD4+CD25+FOXP3+ regulatory T cells after depletion with anti-CD25 monoclonal antibody. / Vignali, Debora; Gürth, Clara-Marie; Pellegrini, Silvia; Sordi, Valeria; Sizzano, Federico; Piemonti, Lorenzo; Monti, Paolo.

In: Transplantation, Vol. 100, No. 9, 23.08.2016, p. 1853 - 1861.

Research output: Contribution to journalArticle

Vignali, Debora ; Gürth, Clara-Marie ; Pellegrini, Silvia ; Sordi, Valeria ; Sizzano, Federico ; Piemonti, Lorenzo ; Monti, Paolo. / IL-7 mediated homeostatic expansion of human CD4+CD25+FOXP3+ regulatory T cells after depletion with anti-CD25 monoclonal antibody. In: Transplantation. 2016 ; Vol. 100, No. 9. pp. 1853 - 1861.
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