Human NKT cells express granulysin and exhibit antimycobacterial activity
Human NKT cells express granulysin and exhibit antimycobacterial activity
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DOI：
10.4049/jimmunol.170.6.3154
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发表时间：
2003-03-15
影响因子：
4.4
通讯作者：
Stenger, S
中科院分区：
文献类型：
--
作者：
Gansert, JL;Kiessler, V;Stenger, S
人类NKT细胞是一种独特的T细胞亚群，表达一种识别非经典Ag呈递分子CD 1d的恒定Valpha 24 TCR。NKT细胞的活化被源自海洋海绵的糖脂α-半乳糖神经酰胺（alphaGalCer）大大增强。由于人单核细胞衍生的细胞表达CD 1d，并且可以携带细胞内病原体结核分枝杆菌，我们询问是否可以使用添加alphaGalCer来诱导NKT细胞对感染的单核细胞、巨噬细胞和单核细胞衍生的树突状细胞的效应功能。NKT细胞分泌IFN-γ，增殖，并响应于α GalCer脉冲的单核细胞衍生的细胞发挥裂解活性。重要的是，α GalCer激活的NKT细胞限制了细胞内M.以CD 1d依赖的方式感染结核病。表现出抗分枝杆菌活性的NKT细胞也表达颗粒溶素，这是一种抗微生物肽，显示通过分枝杆菌表面的扰动介导抗分枝杆菌活性。NKT细胞的脱粒导致颗粒溶解素的耗尽和抗分枝杆菌活性的废除。结核病患者肉芽肿中CD 1d的检测支持NKT细胞与疾病活动部位的CD 1d表达细胞的潜在相互作用。这些研究提供了证据，证明aGalCer。活化的CD 1d限制性T细胞可参与人类宿主对M.肺结核感染。
Human NKT cells are a unique subset of T cells that express an invariant Valpha24 TCR that recognizes the nonclassical Ag-presenting molecule CD1d. Activation of NKT cells is greatly augmented by the marine sponge-derived glycolipid a-galactosylceramide (alphaGalCer). Because human monocyte-derived cells express CD1d and can harbor the intracellular pathogen Mycobacterium tuberculosis, we asked whether the addition of alphaGalCer could be used to induce effector functions of NKT cells against infected monocytes, macrophages, and monocyte-derived dendritic cells. NKT cells secreted IFN-gamma, proliferated, and exerted lytic activity in response to alphaGalCer-pulsed monocyte-derived cells. Importantly, alphaGalCer-activated NKT cells restricted the growth of intracellular M. tuberculosis in a CD1d-dependent manner. NKT cells that exhibited antimycobacterial activity also expressed granulysin, an antimicrobial peptide shown to mediate an antimycobacterial activity through perturbation of the mycobacterial surface. Degranulation of NKT cells resulted in depletion of granulysin and abrogation of antimycobacterial activity. The detection of CD1d in granulomas of tuberculosis patients supports the potential interaction of NKT cells with CD1d-expressing cells at the site of disease activity. These studies provide evidence that aGalCer.;activated CD1d-restricted T cells can participate in human host defense against M. tuberculosis infection.