摘要
Background Activation in vitro of natural killer T （NKT） cells in systemic lupus erythematosus （SLE） with a-galactosylceramide （a-GalCer） and dendritic cells （DC） may affect the immunoregulatory role of NKT cells. This study was designed to compare the number of NKT cells in patients with SLE to the number in healthy volunteers and measure the cytokines secreted from these NKT cells in vitro. Methods Three sets of culture conditions using （i） a-GalCer, （ii） DC, or （iii） both a-GalCer and DC （a-GalCer＋DC） were adopted to expand NKT cells from peripheral blood mononuclear cells （PBMC） of patients with SLE and healthy volunteers. Flow cytometry was used to assess the levels of interleukin （IL）-4, IL-10, interferon （IFN）-y and tumor necrosis factor （TNF）-a produced by the Vα24＋Vβ11＋ NKT cells. Results After 14 days in culture, the total cell count and percentage of Vα24＋Vβ11＋ NKT cells were increased under all conditions but were highest in the a-GalCer＋DC group. The level of IL-4 and IL-10 secreted by Vα24＋Vβ11＋ NKT cells from patients with active SLE was found to be higher than that of inactive patients and the control group （P 〈0.05）, while the levels of IFN-y and TNF-a were lower than those found in the inactive and control groups （P 〈0.05）. Conclusions Va24＋V^11＋ NKT cells showed the greatest expansion in vitro with a-GalCer and DC. Th2-type cytokines from Vα24＋Vβ11＋ NKT cells are the predominant type in patients with SLE, while Th 1 cytokines predominate in the control group. This evolution of NKT cell function during the progression of the disease may have important implications in understanding the mechanism of SLE and for the development of possible therapies using NKT cell agonists.
Background Activation in vitro of natural killer T （NKT） cells in systemic lupus erythematosus （SLE） with a-galactosylceramide （a-GalCer） and dendritic cells （DC） may affect the immunoregulatory role of NKT cells. This study was designed to compare the number of NKT cells in patients with SLE to the number in healthy volunteers and measure the cytokines secreted from these NKT cells in vitro. Methods Three sets of culture conditions using （i） a-GalCer, （ii） DC, or （iii） both a-GalCer and DC （a-GalCer＋DC） were adopted to expand NKT cells from peripheral blood mononuclear cells （PBMC） of patients with SLE and healthy volunteers. Flow cytometry was used to assess the levels of interleukin （IL）-4, IL-10, interferon （IFN）-y and tumor necrosis factor （TNF）-a produced by the Vα24＋Vβ11＋ NKT cells. Results After 14 days in culture, the total cell count and percentage of Vα24＋Vβ11＋ NKT cells were increased under all conditions but were highest in the a-GalCer＋DC group. The level of IL-4 and IL-10 secreted by Vα24＋Vβ11＋ NKT cells from patients with active SLE was found to be higher than that of inactive patients and the control group （P 〈0.05）, while the levels of IFN-y and TNF-a were lower than those found in the inactive and control groups （P 〈0.05）. Conclusions Va24＋V^11＋ NKT cells showed the greatest expansion in vitro with a-GalCer and DC. Th2-type cytokines from Vα24＋Vβ11＋ NKT cells are the predominant type in patients with SLE, while Th 1 cytokines predominate in the control group. This evolution of NKT cell function during the progression of the disease may have important implications in understanding the mechanism of SLE and for the development of possible therapies using NKT cell agonists.
基金
This study was supported by a grant from the Project of Liaoning Province Natural Science Foundation （No. 2007225013）.
