Cross-presentation of disialoganglioside GD3 to natural killer T cells.
Cross-presentation of disialoganglioside GD3 to natural killer T cells.
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DOI：
10.1084/jem.20030446
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发表时间：
2003-07-07
期刊：
影响因子：
--
通讯作者：
Chapman PB
中科院分区：
文献类型：
--
作者：
Wu DY;Segal NH;Sidobre S;Kronenberg M;Chapman PB
GD3是一种表达于人黑色素瘤的神经节苷脂，可被体液免疫系统识别。用人黑色素瘤细胞株SK-MEL-28(GD3+GM2−CD1−)或负载GD3的同基因APC免疫小鼠，均能诱导GD3反应性自然杀伤T(NKT)细胞应答。ELISPOT和负载GD3的小鼠∼四聚体分析显示，免疫小鼠脾细胞中均可检测到GD3反应的NKT细胞，其频率为1：2,000。GD3反应性NKT细胞不与GM2反应，GM2是一种密切相关的神经节苷脂，在未免疫的小鼠中检测不到。GD3反应性NKT细胞最初产生IL-4和干扰素-γ，随后产生IL-10。它们受到CD1d的限制，因为当抗CD1d单抗在负载GD3之前阻断APC或使用CD1d基因敲除小鼠的APC时，反应性被取消。由于SK-MEL-28不表达人CD1的任何异构体，GD3必须在体内被小鼠APC交叉递呈。这是第一次对小鼠NKT细胞的天然配体进行分析，也是第一篇交叉呈现给NKT细胞的权威论文。这可能是NKT细胞识别CD1−肿瘤神经节苷脂的机制之一。
GD3, a ganglioside expressed on human melanoma, can be recognized by the humoral immune system. In this paper, we demonstrate that immunizing mice with the human melanoma cell line SK-MEL-28 (GD3+ GM2− CD1−) or with syngeneic APCs loaded with GD3 can induce a GD3-reactive natural killer T (NKT) cell response. GD3-reactive NKT cells were detected among splenocytes of immunized mice at frequencies of ∼1:2,000 both by ELISPOT and GD3-loaded mouse CD1d tetramer analysis. GD3-reactive NKT cells did not react with GM2, a closely related ganglioside, and were not detectable in unimmunized mice. GD3-reactive NKT cells initially produced IL-4 and IFN-γ followed by IL-10. They were CD1d restricted in that reactivity was abrogated when APCs were blocked with anti-CD1d monoclonal antibody before being loaded with GD3 or when APCs from CD1d knockout mice were used. Because SK-MEL-28 does not express any isoform of human CD1, GD3 must be cross-presented by murine APCs in vivo. This is the first analysis of a natural ligand for mouse NKT cells and the first definitive paper of cross-presentation to NKT cells. This could be a mechanism for NKT cell recognition of tumor gangliosides in CD1− tumors.
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DOI：
10.1084/jem.192.5.741
发表时间：
2000-09-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Matsuda JL;Naidenko OV;Gapin L;Nakayama T;Taniguchi M;Wang CR;Koezuka Y;Kronenberg M
通讯作者：
Kronenberg M
影响因子：
6.5
作者：
Kina, T;Ikuta, K;Katsura, Y
通讯作者：
Katsura, Y
影响因子：
4.4
作者：
Sonoda, KH;Faunce, DE;Stein-Streilein, J
通讯作者：
Stein-Streilein, J
影响因子：
32.4
作者：
Shamshiev, A;Donda, A;De Libero, G
通讯作者：
De Libero, G
影响因子：
56.9
作者：
Moody, DB;Reinhold, BB;Porcelli, SA
通讯作者：
Porcelli, SA