The role for intraepidermal T cells as innate immune cells

表皮内 T 细胞作为先天免疫细胞的作用

基本信息

批准号：
13470175
负责人：
SHIOHARA Tetsuo
金额：
$ 8.32万
依托单位：
Kyorin University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470175/
关键词：
Innate immunity fixed drug eruiption intraepidermal T cells NK cells IL-15 granzyme B perforin innate immunity granzyme B perforin requlatory T細胞 innate immune cells 表面内T細胞 IFN-γ CD69 fucosyltransferase VII CLA

项目摘要

In this study, we asked whether intraepidermal T cells abundantly detected in the resting lesions of fixed drug eruption could display phenotypic properties and functions analogous to innate immune cells, such as NK cells. We found that these T cells were composed of a phenotypically homogeneous population that expresses TCRαβ, CD3, CD8, CD45RA, CD11b, but not CD27 and CD56. This phenotype most closely resembled that of effector memory T cells. Upon stimulation with the causative drug in situ, NKG2D and CD57, frequently expressed on NK cells, were induced to be expressed on some of these intraepidermal T cells. In situ PCR study demonstrated a strong and exclusive induction of IFN-γ mRNA and protein in these T cells with much faster kinetics than their dermal and blood counterparts, upon stimulation in situ. These T cells were also found to have the capacity to kill surrounding keratinocytes through the release of cytotoxic granules, perforin and granzyme B. Thus, these T cells originally evolved to protect tissue integrity can exert an opposite action that is deleterious to the host, when activated in an enhanced or uncontrolled fashion. The activity of these potentially dangerous T cells is therefore carefully controlled to prevent unwanted tissue injury under physiological conditions.

在这项研究中，我们询问在固定药疹的静息病灶中大量检测到的表皮内 T 细胞是否可以表现出类似于天然免疫细胞（例如 NK 细胞）的表型特性和功能，我们发现这些 T 细胞由表型同质的群体组成。表达 TCRαβ、CD3、CD8、CD45RA、CD11b，但不表达 CD27 和 CD56。这种表型与效应记忆 T 细胞最相似。用致病药物进行原位刺激后，NKG2D 和 CD57（通常在 NK 细胞上表达）被诱导在某些表皮内 T 细胞上表达。原位 PCR 研究表明，这些细胞中的 IFN-γ mRNA 和蛋白具有强烈且独特的诱导作用。在原位刺激后，T 细胞的动力学比真皮和血管快得多，这些 T 细胞还被发现能够通过释放细胞毒性颗粒、穿孔素和细胞毒性颗粒来杀死周围的角质形成细胞。因此，这些T细胞最初是为了保护组织完整性而进化的，当以增强或不受控制的方式激活时，它们可以发挥对宿主有害的相反作用。因此，这些潜在危险的T细胞的活性受到仔细控制，以防止不必要的情况。生理条件下的组织损伤。