Rapamycin Modulates the Polarisation of CD4+T Cells Towards TH1 Cells in Patients with Active Granulomatosis with Polyangiitis and Microscopic Polyangiitis

Abstract

Objective: This study investigated whether rapamycin could modulate the polarisation of CD4+ T cells towards TH1, TH2, TH17, and Treg cells using peripheral blood mononuclear cell (PBMC) obtained from patients with granulomatosis with polyangiitis and microscopic polyangiitis (GPA/MPA). Methods: Twenty patients with GPA/MPA were included in this study. Their stored PBMCs were cultured and stimulated with anti-CD3 and anti-CD28 antibodies for 72 h in the presence or absence of rapamycin (10 nM). The cells were stained for surface markers with anti-CD4-FITC and anti-CD25-APC, followed by intracellular staining using anti-interferon (IFN)-gamma-PE, anti-IL-4-PerCP-Cy5, anti-IL17A-APC, and anti-Foxp3-PE. The stained cells were analysed using a flow cytometer. Results: The median age of the 20 GPA/MPA patients (10 men and 10 women) was 65.5 years. Rapamycin treatment significantly modulated the polarisation of CD4+IFN-gamma+ T (TH1) cells compared to no treatment among GPA/MPA patients. In addition, the polarisation of CD4+IFN-gamma+ T (TH1) cells was also significantly reduced in rapamycin-treated PBMC obtained from active patients compared to untreated PBMC from the same patients; however, these alterations were not observed in inactive patients. Conversely, rapamycin treatment did not affect the polarisation of CD4+IL-4+ T (TH2), CD4+IL-17+ T (TH17), or CD4+FoxP3+CD25+ T (Treg) cells, regardless of GPA/MPA activity. Conclusions: This study was the first pilot study to demonstrate that rapamycin modulates the polarisation of CD4+ T cells towards CD4+IFN-gamma+ T cells in active GPA/MPA.