Transplant immunology


Research associate

Paolo Monti


Transplanted organs, tissues and cells are targets of the host immune response, that, in the absence of adequate immunesuppression, lead to graft loss. Host immune response is characterized by the activation and clonal expansion of allo-reactive T cells and, in the case of transplant in subjects with autoimmunity, also of memory auto-reactive clones. Current immunosuppressive regimens used in clinical transplantiation showed limited efficacy and important side effects. The aim of Transplant immunology Unit is to determine mechanisms of proliferation and activation of T cells in clinical transplant to identify novel molecular targets for a selective and effective control of T cell responses in transplantation. In particular, this group aims to determine:

  • the role of memory stem T cells in long term memory maintenance;
  • the role of IL-7 mediated homeostatic proliferation of T cells during immunosuppression therapy;
  • the possibility to control the T cell response with modulators of bio-energetic metabolism (glycolysis, oxidative phosphorylation and glutaminolysis).

Research activity

Our research is focused on novel immune-therapies to control the autoimmune response in T1D and in patients undergoing to islet transplantation.

Current projects: 

  1. Memory stem T cells (Tscm). The main hypothesis is that patients with type 1 diabetes develop Tscm specific for islet antigens, that these cells survive as quiescent cells for years and that they get re-activated by islet transplantation and affect the graft. The aim is to determine the pathogenic role of Tscm in islet transplantation and to identify novel molecular targets for selective inhibition of Tscm. This project is funded by the JDRF (5-CDA-2015-85-A-N)
  2. Targeting GLUT1 to inhibit autoreactive T cells. Upon activation, T cells up-regulate the glucose transporter GLUT1 to fulfill the bio-energetic needs for proliferation. Blocking GLUT1 with small molecules induces T cell exhaustion and unresponsiveness. The clinical translation of this approach would be to design an induction therapy with GLUT1 inhibitors in clinical islet transplantation to prevent autoimmunity recurrence. This project is funded by the JDRF (5-CDA-2015-85-A-N) (2-SRA-2019-756-S-B)
  3. Generation of high-performance regulatory T cells (Treg). Treg are a promising immune-modulatory tool to control autoimmunity, but their efficacy is limited by a short term persistence in vivo. We are generating high-performance Treg with improved survival and lifespan. Starting from naïve Treg precursors, we generate Treg with a stem cell memory phenotype in vitro for adoptively transfer in patients with T1D. This project is funded by the EFSD/JDRF/Lilly European Programme in T1D Research.