The role for intraepidermal T cells as innate immune cells

在这项研究中，我们探讨了在固定性药疹静止期皮损中大量检测到的表皮内T细胞是否具有与天然免疫细胞类似的表型和功能，如NK细胞。我们发现这些T细胞是由一个表型相同的群体组成的，表达TCRCD3、CD8、CD45RA、CD11b，而不表达CD27和CD56。这种表型与效应器记忆T细胞最为相似。在致病药物原位刺激下，NK细胞上表达的NKG2D和CD57在部分表皮内T细胞上表达。原位聚合酶链式反应研究显示，在原位刺激下，这些T细胞能够强烈和特异地诱导干扰素-γ基因和蛋白的表达，而且诱导速度比皮肤和血液中的相应T细胞快得多。这些T细胞还被发现能够通过释放细胞毒颗粒、穿孔素和颗粒酶B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，可以发挥对宿主有害的相反作用。因此，这些潜在危险的T细胞的活动受到仔细的控制，以防止在生理条件下造成不必要的组织损伤。

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.