The Number of NKT and NK Cells in Patients with Systemic Lupus Erythematosus is Decreased: Association with the Pathogenesis for SLE

Kim, Hyun Lee; Kim, Seong Gyun; Kim, Yon Su; Lee, Dong Sup; Jung, Kyeong Cheon; Chung, Jong Hoon; Ahn, Curie; Han, Jin Suk; Kim, Suhnggwon; Lee, Jung Sang; Chung, Doo Hyun

Abstract

BACKGROUND
Systemic lupus erythematosus (SLE) is one of chronic autoimmune diseases of which the central pathophysiologic derangement has not been yet established. Recently, it has been suggested that immune-regulatory cells might affect the development of autoimmune diseases such as SLE and RA. NKT cells were reported to be strong candidate for regulatory cells to regulate immune responses in vivo. To elucidate the roles of immune regulatory cells in the pathogenesis of SLE, we investigated the fractional distribution and functional status of NK and NKT cells in peripheral blood mononuclear cells (PBMC) of SLE patients and healthy volunteers. METHODS: Twenty-two SLE patients and 18 age-matched healthy volunteers were included in this study. The analysis for NK and NKT cells fraction in PBMCs of patients and normal controls were performed by flow cytometric analysis. In addition, to explore the functional status of these cells in SLE patients, we stimulated PBMCs using phorbol ester and ionomycin and measured cytoplasmic IL-4 and IFN-gamma by flow cytometry.
RESULTS
The number (percentage) of NK cells was lower in SLE patients (CD3-CD56+: 4.93+/-1.30%, CD3-CD94+: 4.03+/-1.00%) than in controls (11.28+/-1.77%, 8.15+/-1.40%; p< 0.01, respectively). Peripheral NK cell numbers negatively correlated with anti-dsDNA Ab levels (r=-0.431, p< 0.05) and ESR (r= -0.475, p< 0.05). However, the percentage of these cells was not correlated with renal activity or corticosteroid doses. SLE patients showed, compared with controls, significantly decreased numbers of NKT cells (CD3+CD56+: 1.79+/-0.42% vs 5.04+/-0.44%, CD3+CD94+: 1.21+/-0.27% vs 4.39+/-0.45%; p< 0.01, respectively). The cytoplasmic expression of IL-4 and IFN-gamma in NK and NKT cells of SLE patients stimulated using phorbol ester and ionomycin were almost similar to those of normal controls, suggesting the NKT cells from SLE patients are functionally intact.
CONCLUSION
Our results suggested that the decreased numbers of immune regulatory cells were associated with the immune dysregulation of SLE patients. The cellular replacement of NKT cells may be one of useful therapeutic approaches for autoimmune diseases such as SLE.