Teraki Y, Shiohara T
Department of Dermatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
Br J Dermatol. 2002 Dec;147(6):1118-26. doi: 10.1046/j.1365-2133.2002.05005.x.
Intraepidermal T lymphocytes are a critical element for sustaining the lesional pathology of psoriasis. Integrin alphaEbeta7 (CD103), a ligand for E-cadherin, may play a role in the localization of pathogenic T cells within the epidermis of psoriatic lesions. However, little information is available regarding alphaEbeta7 expression on intraepidermal T cells in psoriasis.
To examine alphaEbeta7 expression on intraepidermal T cells in psoriatic lesions and the regulation of alphaEbeta7 expression on T cells in response to cytokines.
T-cell expression of alphaEbeta7 was examined by immunohistochemistry and flow cytometry. In vitro regulation of alphaEbeta7 expression on CD4+ or CD8+ T cells purified from peripheral blood of healthy donors was also examined.
Immunohistochemical staining revealed expression of alphaEbeta7 on a greater proportion of epidermal T cells than dermal T cells. Nearly 30% of intraepidermal CD4+ T cells were found to express alphaEbeta7 on flow cytometry, whereas more than 80% of intraepidermal CD8+ T cells expressed this integrin. In contrast, few T cells expressed alphaEbeta7 in the peripheral blood of psoriatic patients. The in vitro culture experiment confirmed that alphaEbeta7 was preferentially expressed on CD8+ T cells after stimulation with anti-CD3 monoclonal antibodies. Addition of transforming growth factor-beta and interleukin-4 upregulated alphaEbeta7 expression on T cells, whereas interleukin 12 downregulated this. Furthermore, alphaEbeta7 expression on established memory CD8+ T cells was not so reversible as that on CD4+ T cells.
Preferential and stable expression of alphaEbeta7 on CD8+ T cells may be involved in the lesional pathology of psoriasis.
表皮内T淋巴细胞是维持银屑病皮损病理状态的关键因素。整合素αEβ7（CD103）是E-钙黏蛋白的配体，可能在银屑病皮损表皮内致病性T细胞的定位中发挥作用。然而，关于银屑病表皮内T细胞上αEβ7的表达情况，目前所知甚少。
检测银屑病皮损表皮内T细胞上αEβ7的表达情况以及细胞因子对T细胞上αEβ7表达的调控。
采用免疫组织化学和流式细胞术检测T细胞上αEβ7的表达。同时也检测了从健康供者外周血中纯化得到的CD4⁺或CD8⁺T细胞上αEβ7表达的体外调控情况。
免疫组织化学染色显示，与真皮T细胞相比，表皮T细胞上αEβ7的表达比例更高。流式细胞术检测发现，近30%的表皮内CD4⁺T细胞表达αEβ7，而超过80%的表皮内CD8⁺T细胞表达这种整合素。相比之下，银屑病患者外周血中很少有T细胞表达αEβ7。体外培养实验证实，用抗CD3单克隆抗体刺激后，αEβ7在CD8⁺T细胞上优先表达。添加转化生长因子-β和白细胞介素-4可上调T细胞上αEβ7的表达，而白细胞介素12则下调其表达。此外，已建立的记忆性CD8⁺T细胞上αEβ7的表达不像CD4⁺T细胞上那样容易逆转。
αEβ7在CD8⁺T细胞上的优先和稳定表达可能参与了银屑病的皮损病理过程。
