Rapamycin and Regulatory T Cells in Kidney Transplantation
Summary
The immune system response is mediated by the interaction between the antigen presenting cell (APC), CD4+ T helper cells (Th) and CD4+ CD25+ regulatory T cells, a subgroup of CD4+ T cell which express IL-2 receptor (CD25) and the transcriptional factor foxp3. Regulatory T cell may contribute to the maintenance of tolerance by suppressing the immune response to normal or tumor associated antigens. Regulatory T cell emerge from the thymus during ontogenesis and they represent about 10 % of the peripheral Cd4+ t cells. Rapamycin is one the most use treatment to prevent renal allograft failure. Differently from calcineurin inhibitors (cyclosporine and tacrolimus), that inhibit T-cell activation through the inhibition of calcineurin activation, rapamycin inhibits cellular proliferation by impairing the progression of the cellular cycle, in particular by interaction with mTOR. Recently Battaglia et al. have demonstrated a Treg amplification in murine CD4+ lymphocytes treated with rapamycin in vitro. Aim of the study is to evaluate the effect of different immunosuppressive regimens on regulatory T cell and to verify the hypothesis that rapamycin may induce tolerance in kidney transplanted patients, more than cyclosporine treatment.
Timeline
- Start
- 2008-07
- Primary completion
- 2013-06
- Completion
- 2013-06
Publications
- Background Battaglia M, Stabilini A, Migliavacca B, Horejs-Hoeck J, Kaupper T, Roncarolo MG. Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol. 2006 Dec 15;177(12):8338-47. doi: 10.4049/jimmunol.177.12.8338.
- Background San Segundo D, Fernandez-Fresnedo G, Ruiz JC, Rodrigo E, Benito MJ, Arias M, Lopez-Hoyos M. Two-year follow-up of a prospective study of circulating regulatory T cells in renal transplant patients. Clin Transplant. 2010 May-Jun;24(3):386-93. doi: 10.1111/j.1399-0012.2009.01086.x. Epub 2009 Sep 11.
- Background Ramirez E, Morales JM, Lora D, Mellado M, Cevey M, Alfaro FJ, De Pablos P, Andres A, Paz-Artal E, Serrano A. Peripheral blood regulatory T cells in long-term kidney transplant recipients. Transplant Proc. 2009 Jul-Aug;41(6):2360-2. doi: 10.1016/j.transproceed.2009.05.007.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Cyclosporine | Peptide | — | — |
| Subject | Rapamycin | Small molecule | — | — |
Indications
No indication recorded.