Numerical and functional deficiencies of natural killer T cells in systemic lupus erythematosus: their deficiency related to disease activity

Abstract

Objective. This study was designed to examine the frequency of natural killer T (NKT) cells and the response to alpha-galactosylceramide (alpha-GalCer) in SLE patients and to investigate the clinical relevance of NKT cell levels. Methods. Patients with SLE (n = 128) and age- and sex-matched healthy controls (HCs) (n = 92) were enrolled in the study. NKT cell and CD1d levels were measured by flow cytometry. Gene expression was determined by RT-PCR, and cytokine secretion by multiple cytokine assay. Peripheral blood mononuclear cells (PBMCs) were cultured in vitro with alpha-GalCer. Proliferation indices of NKT cells were estimated by flow cytometry. Results. Percentages and absolute numbers of NKT cells were significantly lower in the peripheral blood of SLE patients than in that of HCs, whereas CD1d levels in PBMCs were comparable between these two groups. Notably, this NKT cell deficiency was found to be correlated with SLEDAI. NKT cell proliferation was found to be impaired in SLE patients, and cytokine production by NKT cells in response to alpha-GalCer was diminished. This poor responsiveness to alpha-GalCer was found to be due to NKT cell dysfunction rather than to an abnormality in CD1d-expressing cells. Conclusions. Our data show that NKT cell levels and functions are defective in SLE patients. Furthermore, these deficiencies were found to reflect disease activity. It would appear that these NKT cell abnormalities could contribute to immune system dysregulation in SLE.