Rapamycin induces ILT3ILT4 dendritic cells promoting a new immunoregulatory pathway.
Stallone G, Pontrelli P, et al.Kidney International 2013; 85(4): 888-897.
Aims
To investigate whether chronic exposure to rapamycin may induce the upregulation of ILT3 and ITL4 on dendritic cells (DC) and trigger the differentiation of CD8+ CD28-T cells, potentially promoting an increase in regulatory T cells.
Interventions
Patients were assigned to a 40% dose reduction of a calcineurin inhibitor (CNI) plus MMF and corticosteroids or withdrawal of CNI plus MMF and rapamycin.
Participants
40 renal transplant patients with biopsy-proven chronic allograft neuropathy receiving CNI.
Outcomes
The outcomes included clinical and histological features, circulating DC subsets, circulating T cell populations, ILT3/ITL4 expression and Th1/Th2 balance within graft.
Follow-up
2 years.
CET Conclusions
This paper reports an interesting substudy from a clinical RCT of CNI minimisation compared to mTOR (rapamycin) conversion in a group of renal transplant recipients with chronic allograft nephropathy. The authors demonstrate that conversion to rapamycin is associated with an increase in ILT3 and ILT4 expressing dendritic cells, and also with expansion of the Treg and CD8+CD28- T cell population. The two effects are correlated, leading the authors to conclude that the use of rapamycin may promote immunoregulation in this clinical setting.
Data analysis
Modified intention-to-treat analysis
Quality notes
Previously assessed in Stallone et al. Rapamycin for treatment of chronic allograft nephropathy in renal transplant patients. Journal of American Society of Nephrology 2005;16:3755-3762
Trial registration
Not reported