A potent adjuvant effect of a CD1d-binding NKT cell ligand in human immune system mice.

A potent adjuvant effect of a CD1d-binding NKT cell ligand in human immune system mice.
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DOI:
10.1080/14760584.2017.1256208
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发表时间:
2017-01
影响因子:
6.2
通讯作者:
Tsuji M
Tsuji M
中科院分区:
医学2区
文献类型:
--
作者:
Li X;Huang J;Kaneko I;Zhang M;Iwanaga S;Yuda M;Tsuji M

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一种CD1d结合的不变自然杀伤T(INKT)细胞刺激性糖脂,即7DW8-5,被证明能增强辐射减弱子孢子(RAS)疟疾疫苗在小鼠中的效力。在目前的研究中,我们的目标是确定7DW8-5是否能够在人类免疫系统(HIS)小鼠中显示出强大的佐剂作用。His-A2/hCD1d小鼠是由携带编码人类CD1d分子和人类白细胞抗原A*0201基因的腺相关病毒血清9型NSG小鼠转导,然后植入人造血干细胞而产生的,具有功能性人iNKT细胞和CD8+T细胞。用人CD1d四聚体和人HLA-A*0201四聚体分别测定His-A2/hCD1d小鼠体内人iNKT细胞对7DW8-5和人类白细胞抗原A*0201限制性的人CD8+T细胞对人疟疾抗原的反应量。我们发现,7DW8-5在体外刺激His-A2/hCD1d小鼠和His-A2/hCD1d小鼠来源的人iNKT细胞。我们还发现,7DW8-5显著增加了His-A2/hCD1d小鼠体内人类疟疾抗原特异性HLA-A*0201限制性的人CD8+T细胞反应水平。我们的研究表明,7DW8-5可以通过增强疟疾特异性的人CD8+T细胞应答而对RAS疫苗诱导的抗疟疾免疫表现出强大的佐剂作用。
A CD1d-binding invariant natural killer T (iNKT)-cell stimulatory glycolipid, namely 7DW8–5, is shown to enhance the efficacy of radiation-attenuated sporozoites (RAS)-based malaria vaccine in mice. In the current study, we aim to determine whether 7DW8-5 can display a potent adjuvant effect in human immune system (HIS) mice. HIS-A2/hCD1d mice, which possess both functional human iNKT cells and CD8+ T cells, were generated by the transduction of NSG mice with adeno-associated virus serotype 9 expressing genes that encode human CD1d molecules and HLA-A*0201, followed by the engraftment of human hematopoietic stem cells. The magnitudes of human iNKT-cell response against 7DW8-5 and HLA-A*0201-restricted human CD8+ T-cell response against a human malaria antigen in HIS-A2/hCD1d mice were determined by using human CD1d tetramer and human HLA-A*0201 tetramer, respectively. We found that 7DW8-5 stimulates human iNKT cells in HIS-A2/hCD1d mice, as well as those derived from HIS-A2/hCD1d mice in vitro. We also found that 7DW8-5 significantly increases the level of a human malarial antigen-specific HLA-A*0201-restricted human CD8+ T-cell response in HIS-A2/hCD1d mice. Our study indicates that 7DW8-5 can display a potent adjuvant effect on RAS vaccine-induced anti-malarial immunity by augmenting malaria-specific human CD8+ T-cell response.
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