Direct Evidence for Interferon- (cid:1) Production by Effector-Memory-Type Intraepidermal T Cells Residing at an Effector Site of Immunopathology in Fixed Drug Eruption
Direct Evidence for Interferon- (cid:1) Production by Effector-Memory-Type Intraepidermal T Cells Residing at an Effector Site of Immunopathology in Fixed Drug Eruption
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发表时间：
2002
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通讯作者：
Y. Mizukawa;Y. Yamazaki;Y. Teraki;J. Hayakawa;K. Hayakawa;H. Nuriya;M. Kohara;T. Shiohara
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作者：
Y. Mizukawa;Y. Yamazaki;Y. Teraki;J. Hayakawa;K. Hayakawa;H. Nuriya;M. Kohara;T. Shiohara
免疫记忆T细胞被战略性地放置在上皮组织中，以提供针对病原体的前线免疫保护。然而，由于在病理环境中对这些T细胞进行采样存在困难，因此很少研究它们的有害影响。我们以前的研究表明，在固定型药疹（药物引起的皮肤病的局部变异）的病变中，表皮内CD 8（cid：1）T细胞的类似亚群以高频率持续存在。在原位激活的这一子集导致局部表皮损伤，可以追溯到抗原攻击后的病变，成对的免疫组化染色，逆转录酶-聚合酶链反应原位，和流式细胞术的分散细胞。在这里，我们表明，效应记忆T细胞在这些表皮内的CD 8（cid：1）T细胞，但不是真皮和循环的同行大大丰富，他们组成型表达早期活化标记CD 69，甚至在挑战。令人惊讶的是，这些T细胞中的大部分表达了即时效应子功能，如通过原位快速产生高水平的干扰素-（cid：2）所证明的，在攻击后，在mRNA和蛋白质水平上具有比它们的对应物快得多的动力学。其次是局部表皮损伤。离体细胞内细胞因子测定显示，这些分散的T细胞中的绝大多数产生干扰素-（cid：2）。这项研究提供了第一个现场描述的有害影响，具体
Effector-memory T cells are strategically placed to epithelial tissues to provide frontline immune protection against pathogens. Their detrimental effects, however, have been rarely examined because of dif-ficulty in sampling these T cells in pathological settings. Our previous studies suggested persistence of a similar subset of intraepidermal CD8 (cid:1) T cells at high frequencies in the lesions of fixed drug eruption, a localized variant of drug-induced dermatoses. In situ activation of this subset resulting in localized epidermal injury can be traced in the lesions after antigen challenge by paired immunohistochemical staining, reverse transcriptase-polymerase chain reaction in situ , and flow cytometry of dispersed cells. Here we show that effector-memory T cells were greatly enriched in these intraepidermal CD8 (cid:1) T cells, but not dermal and circulating counterparts, and that they constitutively express an early activation marker CD69 even before challenge. Surprisingly, a large proportion of these T cells expressed immediate effector function as evidenced by the rapid production of high levels of interferon- (cid:2) in situ with much faster kinetics than their counterparts at the mRNA and protein levels after challenge. This was followed by localized epidermal injury. The intracellular cytokine assay ex vivo shows that the great majority of these dispersed T cells produce interferon- (cid:2) . This study provides the first in situ description of the detrimental effects specifically