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

3 Citations (Scopus)

Abstract

BACKGROUND: 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-CD25 monoclonal 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+ T cells as CD25 is also rapidly downregulated and internalized. Regulatory T-cell reconstitution is completed within 6 months posttransplantation and appeared to be driven by IL-7–mediated homeostatic T-cell 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
JournalTransplantation
DOIs
Publication statusAccepted/In press - Jun 14 2016

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

ASJC Scopus subject areas

  • Transplantation

Cite this

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, 14.06.2016.

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.
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AU - Vignali, Debora

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AU - Pellegrini, Silvia

AU - Sordi, Valeria

AU - Sizzano, Federico

AU - Piemonti, Lorenzo

AU - Monti, Paolo

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