Berzofsky Jay A, Terabe Masaki
Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1578, USA.
Curr Mol Med. 2009 Aug;9(6):667-72. doi: 10.2174/156652409788970706.
NKT cells are true T cells that serve as a bridge between the innate and adaptive immune system, acting as first responders. They recognize lipid antigens rather than peptides, and respond to these when presented by a non-classical class I MHC molecule, CD1d. NKT cells can play a pathogenic role in asthma or a protective role against several autoimmune diseases, in part based on their cytokine profile. In cancer, they can play opposite roles, contributing to anti-tumor immunity or suppressing it. The protective NKT cells were found to be primarily type I NKT cells defined by use of a semi-invariant T cell receptor involving Valpha14Jalpha18 in mice and Valpha24Jalpha18 in humans and responding to alpha-galactosylceramide, and the most protective were among the minority that are CD4-. The suppressive NKT cells were found to be CD4+ and to be primarily type II NKT cells, that have diverse T-cell receptors and respond to other lipids. Further, the type I and type II NKT cells were found to counter-regulate each other, forming a new immunoregulatory axis. This axis may have broad implications beyond cancer, as NKT cells play a role in steering other adaptive immune responses. The balance along this axis could affect immunity to tumors and infectious diseases and responses to vaccines.
自然杀伤T细胞（NKT细胞）是真正的T细胞，作为先天免疫系统和适应性免疫系统之间的桥梁，充当第一反应者。它们识别脂质抗原而非肽抗原，当由非经典的I类主要组织相容性复合体分子CD1d呈递这些抗原时做出反应。NKT细胞在哮喘中可发挥致病作用，或在几种自身免疫性疾病中发挥保护作用，部分基于其细胞因子谱。在癌症中，它们可发挥相反作用，有助于抗肿瘤免疫或抑制抗肿瘤免疫。已发现具有保护作用的NKT细胞主要是I型NKT细胞，其通过使用涉及小鼠中Valpha14Jalpha18和人类中Valpha24Jalpha18的半不变T细胞受体来定义，并对α-半乳糖神经酰胺做出反应，其中最具保护作用的是少数CD4阴性细胞。已发现具有抑制作用的NKT细胞是CD4阳性，主要是II型NKT细胞，它们具有多样的T细胞受体并对其他脂质做出反应。此外，发现I型和II型NKT细胞相互拮抗调节，形成一个新的免疫调节轴。由于NKT细胞在引导其他适应性免疫反应中发挥作用，该轴可能具有超出癌症范畴的广泛影响。沿着这个轴的平衡可能会影响对肿瘤和传染病的免疫以及对疫苗的反应。
