Prolonged IFN-γ-producing NKT response induced with α-galactosylceramide-loaded DCs
Prolonged IFN-γ-producing NKT response induced with α-galactosylceramide-loaded DCs
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DOI：
10.1038/ni827
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发表时间：
2002-09-01
影响因子：
30.5
通讯作者：
Steinman, RM
中科院分区：
文献类型：
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作者：
Fujii, S;Shimizu, K;Steinman, RM
自然杀伤T(NKT)淋巴细胞介导对糖脂药物半乳糖神经酰胺(AlphaGalCer)的快速反应，该反应在12小时内触发大量细胞因子释放到血清中，从白细胞介素4(IL-4)开始。当用树突状细胞(DC)给小鼠注射AlphaGalCer时，反应更持久(4天)，以产生干扰素-伽马的NKT细胞大量扩张为标志，并对B16黑色素瘤的转移具有更强的抵抗力。然而，来自给予游离α-GalCer的小鼠的DC在转移到未出生的小鼠身上时能够诱导强烈的产生干扰素-γ的NKT反应，但当转移到α-GalCer治疗的接受者身上时则不能。在后者中，NKT细胞是无能的，只有在补充IL-2的情况下才能对糖脂产生反应。因此，当AlphaGalCer选择性地靶向DC时，小鼠产生更强、更持久和效应型的NKT反应，但这种反应可以被其他细胞呈递AlphaGalCer后诱导的无能所阻断。
Natural killer T (NKT) lymphocytes mediate a rapid reaction to the glycolipid drug galactosylceramide (alphaGalCer), which triggers release of large amounts of cytokines into the serum within 12 h, starting with interleukin 4 (IL-4). When alphaGalCer is administered to mice on dendritic cells (DCs) instead, the response is more prolonged (> 4 days) and marked by a large expansion in IFN-gamma-producing NKT cells as well as greater resistance to metastases of the B16 melanoma. Nevertheless, DCs from mice given free alphaGalCer are able to induce strong IFN-gamma-producing NKT responses when transferred to naive mice, but not when transferred to alphaGalCer-treated recipients. In the latter, the NKT cells are anergized and can respond to glycolipid only in the presence of supplemental IL-2.Therefore, when alphaGalCer is selectively targeted to DCs, mice develop a stronger, more prolonged and effector type of NKT response, but this response can be blocked by the induction of anergy after presentation of alphaGalCer on other cells.