Nishio Daisuke, Izu Kunio, Kabashima Kenji, Tokura Yoshiki
Department of Dermatology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Kitakyushu 807-8555, Japan.
J Dermatol Sci. 2007 Oct;48(1):25-33. doi: 10.1016/j.jdermsci.2007.05.013. Epub 2007 Jun 29.
In the non-immediate type of drug eruptions, the populations of circulating T cells may be altered as a consequence of T cell responses to a culprit drug.
The aim of this study was to investigate differences among the types of drug eruptions in propagating T cell populations of the patients' peripheral blood.
The type of eruptions were divided into three categories: (1) generalized maculopapular eruption (MPE), (2) erythema multiforme (EM)/Stevens-Johnson syndrome (SJS), and (3) drug-induced hypersensitivity syndrome (DIHS) or drug rash with eosinophilia and systemic symptoms (DRESS). T cell populations were phenotypically analyzed by flow cytometry in the percentage of T helper (Th) 1 (CXCR3+CD4+), Th2 (CCR4+CD4+), Tc1 (CXCR3+CD8+), and Tc2 (CCR4+CD8+) subsets and their activation states as assessed by CD69, CD25 or HLA-DR positivity.
Upon occurrence of both MPE and EM/SJS, Th2 cells outnumbered Th1 cells, whereas Tc1 and Tc2 cells differentially predominated in EM/SJS and MPE, respectively. An increase of HLA-DR+CD8+ cells in EM/SJS type provided another supportive evidence for Tc1 stimulation. In DIHS, during the development of the second wave of eruption and/or liver dysfunction associated with anti-HHV6 antibody elevation, CD4+ cells were gradually decreased, but CD8+ cells were inversely increased. Tc1 cells were increased as well as Th1 cells. Finally, in all the three groups, there existed a considerable number of CD25+CTLA-4-CD4+ T cells.
Our study suggests that Th2/Tc2 and Th2/Tc1 cells mediate MPE and EM/SJS, respectively, and Tc1 cells are involved in the pathogenesis of DIHS at the late stage.
在非速发型药物疹中，循环T细胞群体可能因T细胞对致病药物的反应而发生改变。
本研究旨在调查患者外周血中增殖性T细胞群体在不同类型药物疹中的差异。
将皮疹类型分为三类：（1）泛发性斑丘疹（MPE），（2）多形红斑（EM）/史蒂文斯-约翰逊综合征（SJS），以及（3）药物性超敏反应综合征（DIHS）或伴有嗜酸性粒细胞增多和全身症状的药物疹（DRESS）。通过流式细胞术对T细胞群体进行表型分析，检测辅助性T细胞（Th）1（CXCR3+CD4+）、Th2（CCR4+CD4+）、细胞毒性T细胞（Tc）1（CXCR3+CD8+）和Tc2（CCR4+CD8+）亚群的百分比及其通过CD69、CD25或HLA-DR阳性评估的激活状态。
在MPE和EM/SJS发生时，Th2细胞数量超过Th1细胞，而Tc1和Tc2细胞分别在EM/SJS和MPE中占优势。EM/SJS型中HLA-DR+CD8+细胞的增加为Tc1刺激提供了另一个支持证据。在DIHS中，在与抗HHV6抗体升高相关的第二波皮疹和/或肝功能障碍发展过程中，CD4+细胞逐渐减少，但CD8+细胞则相反增加。Tc1细胞和Th1细胞均增加。最后，在所有三组中，都存在相当数量的CD25+CTLA-4-CD4+T细胞。
我们的研究表明，Th2/Tc2和Th2/Tc1细胞分别介导MPE和EM/SJS，并且Tc1细胞在DIHS后期的发病机制中起作用。
