Functions of NKT cell autoreactivity

NKT细胞是一种独特的T淋巴细胞，已知能发挥强大的免疫调节作用 影响，尽管它们影响免疫的机制 人们并不能很好地理解他们的反应。与大多数其他类型的T细胞不同，NKT细胞可以 被CD1d分子呈递的自身抗原激活。这种类型的 自身反应性刺激可能是NKT细胞的主要方式之一 在体内被激活。然而，人类NKT细胞识别的自身抗原仍然存在 特征不佳，对功能后果知之甚少 NKT细胞的自身反应激活。根据我们的初步数据，我们假设 脂类信使，如溶血磷脂，是NKT细胞的自身抗原， 这为体内NKT细胞的激活提供了一条直接 与更广泛的免疫调节过程有关。另外，我们最近有 显示NKT细胞可诱导外周血单核细胞分化为未成熟 DC，我们目前的数据表明，由此产生的DC具有独特的监管 功能。因此，我们假设NKT细胞影响下游免疫。 调节髓系树突状细胞分化和功能特性的反应。 在这里，我们建议：i)鉴定由人NKT细胞识别的自身抗原， 分析CD1d自身抗原呈递的分子要求； 2)研究生理脂质信使对NKT细胞自身反应性的调节； 以及iii)检查髓系树突状细胞的特性 对NKT细胞信号的反应。

NKT cells are unique T lymphocytes that are known to exert potent immunomodulatory effects, although the mechanisms by which they influence immune responses are not well understood. Unlike most other types of T cells, NKT cells can be functionally activated by self antigens presented by CD1d molecules. This type of autoreactive stimulation is likely to be one of the primary ways that NKT cells are activated in vivo. However, the self antigens recognized by human NKT cells remain poorly characterized, and there is little understanding of the functional consequences of NKT cell autoreactive activation. Based on our preliminary data, we hypothesize that lipid messengers, such as lyso-phospholipids, are auto-antigens for NKT cells, and that this provides a pathway by which NKT cell activation in vivo is directly connected to broader processes of immune regulation. Additionally, we have recently shown that NKT cells induce peripheral blood monocytes to differentiate into immature DCs, and our current data suggests the resulting DCs have distinctive regulatory functions. Hence, we hypothesize that NKT cells influence down-stream immune responses by regulating the differentiation and functional properties of myeloid DCs. Here, we propose: i) to Identify auto-antigens recognized by human NKT cells, and to analyze the molecular requirements for CD1d auto-antigen presentation; ii) to Investigate regulation of NKT cell autoreactivity by physiological lipidmessengers; and iii) to examine the properties of myeloid DC that differentiate in response to NKT cell signals.