Article Text
Abstract
Background Systemic sclerosis (SSc) is a rare and heterogeneous immune-mediated disease. Its complex pathogenesis remains incompletely understood. Invariant natural killer T (iNKT) cells have been discussed in several autoimmune diseases1. They recognise selected endogenous as well as synthetic glycolipids like α-galactosylceramide by their TCR with high affinity and when activated, they typically release high amounts of pro- and/or anti-inflammatory cytokines2.
Objectives To evaluate numbers and function of invariant natural killer T cells in patients with systemic sclerosis and analyse their correlation with disease parameters.
Methods Human iNKT cells from 91 patients with SSc and 23 healthy controls were analysed by flow cytometric analysis. Their proliferative capacity and cytokine production was investigated following activation with CD1d ligand α-GalCer.
Results We observed an absolute and relative decrease of iNKT cells in patients with SSc (0.036 iNKT cells/106 lymphocytes) compared with healthy controls (0.159 iNKT cells/106 lymphocytes, p<0.001). We could also demonstrate that iNKT cells from patients with SSc showed a significantly decreased expansion capacity upon stimulation with α-GalCer. Interestingly, there was no difference concerning the subtype of SSc, disease severity or whether patients received immunosuppressive drugs.
Conclusions iNKT cells are deficient and functionally impaired in patients with SSc. Therefore, adoptive transfer strategies using culture-expanded iNKT cells or administration of glycosphingolipids such as α-GalCer could be a novel approach to treat SSc patients.
References [1] Wu L, Van KL. Natural killer T cells and autoimmune disease. Curr Mol Med2009;9:4–14.
[2] Bendelac A, Savage PB, Teyton L. The biology of NKT cells. Annu Rev Immunol. 2007;25:297–336.
Acknowledgements The National Institutes of Health Tetramer Core Facility kindly provided CD1d tetramer reagents. We would like to thank the Flow Cytometry Core Facility Berg of the University Hospital Tübingen for their excellent technical support.
Disclosure of Interest None declared