Sirolimus vs cyclosporine after induction with basiliximab does not promote regulatory T cell expansion in de novo kidney transplantation: Results from a single-center randomized trial

Carmelo Libetta, Pasquale Esposito, Marilena Gregorini, Elisa Margiotta, Claudia Martinelli, Ilaria Borettaz, Michele Canevari, Teresa Rampino, Elena Ticozzelli, Massimo Abelli, Federica Meloni, Antonio Dal Canton

Research output: Contribution to journalArticle

Abstract

Regulatory T cells (Tregs), defined as CD4 + CD25 + highFoxP3 + CD127 - cells, could promote tolerance in renal transplantation (Tx).In an open-label, randomized, controlled trial 62 de-novo Tx recipients received induction with basiliximab and cyclosporine A (CsA) for the first month after Tx and then were assigned to treatment with sirolimus (SRL) or CsA and followed up for 2. years.The primary endpoint was to evaluate the effects of induction and maintenance treatments on circulating Tregs, while the secondary endpoint was the assessment of Treg renal infiltration and the relationship between Treg count and clinical outcomes.There were no significant differences in either circulating or tissue Treg number between the two groups. At 1. month post-Tx, all patients presented a profound Treg depletion, followed by a significant increase in Tregs that resulted stable during the follow-up. The same trend was also observed for non-activated Tregs (CD69 -) and for other immunocompetent cells (CD4. + and CD8. + T cells, B cells and NK cells). Moreover, the Treg count did not correlate either with renal function or with acute rejection and graft loss.Initial immunosuppression is crucial to regulate circulating Tregs, regardless of subsequent immunosuppressive maintenance regimens. Strategies aiming to promote tolerance should consider the effects of different induction regimens.

Original languageEnglish
Article number992
Pages (from-to)117-124
Number of pages8
JournalTransplant Immunology
Volume33
Issue number2
DOIs
Publication statusPublished - Oct 1 2015

Keywords

  • Basiliximab
  • Cyclosporine A
  • Kidney transplant
  • Regulatory T cells
  • Sirolimus
  • Transplant outcomes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Transplantation

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