Sustained expansion of NKT cells and antigen-specific T cells after injection of alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients.
Sustained expansion of NKT cells and antigen-specific T cells after injection of alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients.
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DOI：
10.1084/jem.20042592
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发表时间：
2005-05-02
期刊：
影响因子：
--
通讯作者：
Dhodapkar MV
中科院分区：
文献类型：
--
作者：
Chang DH;Osman K;Connolly J;Kukreja A;Krasovsky J;Pack M;Hutchinson A;Geller M;Liu N;Annable R;Shay J;Kirchhoff K;Nishi N;Ando Y;Hayashi K;Hassoun H;Steinman RM;Dhodapkar MV
自然杀伤T（NKT）细胞是不同的糖脂反应性先天淋巴细胞，其涉及对病原体和肿瘤的抗性。早期尝试动员NKT细胞，特别是在人体内，取得了有限的成功。在这里，我们评估了静脉注射单核细胞衍生的成熟DC，负载合成NKT细胞配体，α-半乳糖神经酰胺（α-GalCer; KRN-7000）在5例晚期癌症患者中。注射α-GalCer脉冲的而不是未脉冲的树突状细胞（DC）导致所有患者中NKT细胞的几个亚群扩增>100倍;这些可以在疫苗接种后长达6个月检测到。NKT激活与血清白细胞介素-12 p40和IFN-γ诱导蛋白-10水平的升高相关。此外，体内巨细胞病毒特异性记忆性CD 8 + T细胞对α-GalCer负载的DC有反应，但未脉冲的DC没有反应。这些数据证明了NKT细胞在人体（包括晚期癌症患者）体内持续扩增的可行性，并表明NKT激活可能有助于增强体内适应性T细胞免疫。
Natural killer T (NKT) cells are distinct glycolipid reactive innate lymphocytes that are implicated in the resistance to pathogens and tumors. Earlier attempts to mobilize NKT cells, specifically, in vivo in humans met with limited success. Here, we evaluated intravenous injection of monocyte-derived mature DCs that were loaded with a synthetic NKT cell ligand, α-galactosyl-ceramide (α-GalCer; KRN-7000) in five patients who had advanced cancer. Injection of α-GalCer–pulsed, but not unpulsed, dendritic cells (DCs) led to >100-fold expansion of several subsets of NKT cells in all patients; these could be detected for up to 6 mo after vaccination. NKT activation was associated with an increase in serum levels of interleukin-12 p40 and IFN-γ inducible protein-10. In addition, there was an increase in memory CD8+ T cells specific for cytomegalovirus in vivo in response to α-GalCer–loaded DCs, but not unpulsed DCs. These data demonstrate the feasibility of sustained expansion of NKT cells in vivo in humans, including patients who have advanced cancer, and suggest that NKT activation might help to boost adaptive T cell immunity in vivo.
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影响因子：
2.2
作者：
Fujii, S;Shimizu, K;Dhodapkar, MV
通讯作者：
Dhodapkar, MV
影响因子：
4.4
作者：
Eberl, G;Brawand, P;MacDonald, HR
通讯作者：
MacDonald, HR
影响因子：
4
作者：
Berzins, SP;Kyparissoudis, K;Godfrey, DI
通讯作者：
Godfrey, DI
影响因子：
30.5
作者：
Fujii, S;Shimizu, K;Steinman, RM
通讯作者：
Steinman, RM
影响因子：
4.4
作者：
Gadola, SD;Dulphy, N;Cerundolo, V
通讯作者：
Cerundolo, V