α-糖基神经酰胺以CD1d限制和Valpha24TCR介导的方式激活人Valpha24 NKT细胞。

Activation of human Valpha24NKT cells by alpha-glycosylceramide in a CD1d-restricted and Valpha24TCR-mediated manner.

作者信息

Nieda M, Nicol A, Koezuka Y, Kikuchi A, Takahashi T, Nakamura H, Furukawa H, Yabe T, Ishikawa Y, Tadokoro K, Juji T

机构信息

Department of Research, The Japanese Red Central Blood Center, Tokyo.

出版信息

Hum Immunol. 1999 Jan;60(1):10-9. doi: 10.1016/s0198-8859(98)00100-1.

DOI:10.1016/s0198-8859(98)00100-1

PMID:9952023

Abstract

Vact14NK(natural killer) T cells play an important role in controlling tumors or in preventing autoimmunity in the murine system. Valpha24NKT cells, the human counterpart of Valpha14NKT cells, may contribute to controlling the progression of autoimmune diseases in humans. These findings show the possibility that ligand(s) for these NKT cells can control the above-mentioned pathological conditions. Specific glycolipids such as alpha-galactosylceramide (alpha-GalCer) and alpha-glucosylceramide (alpha-GlcCer) have been identified as ligand(s) recognized by murine Valpha14NKT cells in a CD1d-restricted manner, but it remains unclear whether these glycolipids are ligand(s) for Valpha24NKT cells in humans. To determine whether alpha-glycosylceramide is presented by CD1d molecules in humans, we initially established a Valpha24NKT cell line specific for alpha-glycosylceramide using dendritic cell (DC) like cells from normal peripheral blood mononuclear cells (PBMC) in an autologous mixed leukocyte reaction (auto-MLR) system, and characterized the Valpha24NKT cell line. The Valpha24NKT cells were CD3+ CD4-CD8-Valpha24+Vbeta11+NKRP1A+ and specifically proliferated in response to alpha-glycosylceramide in CD1d-restricted and Valpha24TCR-mediated manner. The phenotypic and functional similarities between murine Valpha14NKT cells and human Valpha24NKT cells suggest that Valpha24NKT cells may play an important role in controlling tumors or in preventing autoimmunity as observed with Valpha14NKT cells.

摘要

Vα14自然杀伤（NK）T细胞在小鼠系统中对控制肿瘤或预防自身免疫发挥重要作用。Vα24NKT细胞是Vα14NKT细胞的人类对应物，可能有助于控制人类自身免疫疾病的进展。这些发现表明，这些NKT细胞的配体有可能控制上述病理状况。特定的糖脂，如α-半乳糖神经酰胺（α-GalCer）和α-葡萄糖神经酰胺（α-GlcCer），已被确定为小鼠Vα14NKT细胞以CD1d限制性方式识别的配体，但这些糖脂是否是人类Vα24NKT细胞的配体仍不清楚。为了确定α-糖基神经酰胺是否由人类的CD1d分子呈递，我们最初在自体混合淋巴细胞反应（auto-MLR）系统中，使用来自正常外周血单核细胞（PBMC）的树突状细胞（DC）样细胞，建立了对α-糖基神经酰胺特异的Vα24NKT细胞系，并对该Vα24NKT细胞系进行了表征。Vα24NKT细胞为CD3+CD4 - CD8 - Vα24+Vβ11+NKRP1A+，并以CD1d限制性和Vα24TCR介导的方式对α-糖基神经酰胺特异性增殖。小鼠Vα14NKT细胞和人类Vα24NKT细胞在表型和功能上的相似性表明，Vα24NKT细胞可能如Vα14NKT细胞一样，在控制肿瘤或预防自身免疫中发挥重要作用。