Birkholz Alysia M, Kronenberg Mitchell
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, USA; Division of Biological Sciences, University of California, San Diego, La Jolla, USA.
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, USA; Division of Biological Sciences, University of California, San Diego, La Jolla, USA.
Biomed J. 2015 Dec;38(6):470-83. doi: 10.1016/j.bj.2016.01.003. Epub 2016 Mar 10.
Natural killer T-cells, with an invariant T-cell antigen receptor α-chain (iNKT cells), are unique and conserved subset of lymphocytes capable of altering the immune system through their rapid and potent cytokine responses. They are reactive to lipid antigens presented by the CD1d molecule, an antigen-presenting molecule that is not highly polymorphic. iNKT cell responses frequently involve mixtures of cytokines that work against each other, and therefore attempts are underway to develop synthetic antigens that elicit only strong interferon-gamma (IFNγ) or only strong interleukin-4 responses but not both. Strong IFNγ responses may correlate with tighter binding to CD1d and prolonged stimulation of iNKT cells, and this may be useful for vaccine adjuvants and for stimulating anti-tumor responses. iNKT cells are self-reactive although the structure of the endogenous antigen is controversial. By contrast, bacterial and fungal lipids that engage the T-cell receptor and activate IFNγ from iNKT cells have been identified from both pathogenic and commensal organisms and the responses are in some cases highly protective from pathogens in mice. It is possible that the expanding knowledge of iNKT cell antigens and iNKT cell activation will provide the basis for therapies for patients suffering from infectious and immune diseases and cancer.
自然杀伤T细胞，其T细胞抗原受体α链不变（iNKT细胞），是淋巴细胞中独特且保守的亚群，能够通过其快速且强效的细胞因子反应改变免疫系统。它们对由CD1d分子呈递的脂质抗原具有反应性，CD1d是一种多态性不高的抗原呈递分子。iNKT细胞反应常常涉及相互拮抗的细胞因子混合物，因此人们正在尝试开发仅引发强烈干扰素-γ（IFNγ）或仅引发强烈白细胞介素-4反应而非两者兼具的合成抗原。强烈的IFNγ反应可能与与CD1d的更紧密结合以及iNKT细胞的延长刺激相关，这对于疫苗佐剂和刺激抗肿瘤反应可能有用。iNKT细胞具有自身反应性，尽管内源性抗原的结构存在争议。相比之下，已从致病和共生生物体中鉴定出与T细胞受体结合并激活iNKT细胞产生IFNγ的细菌和真菌脂质，并且在某些情况下，这些反应对小鼠病原体具有高度保护作用。对iNKT细胞抗原和iNKT细胞激活的不断扩展的认识有可能为患有感染性疾病、免疫疾病和癌症的患者提供治疗基础。
