Schechner J S, Edelson R L, McNiff J M, Heald P W, Pober J S
Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut 06520-8059, USA.
Lab Invest. 1999 May;79(5):601-7.
Integrin alpha4beta7 has been associated with tissue-specific homing of malignant and inflammatory lymphocytes to gastrointestinal mucosa, whereas integrin alphaEbeta7 has been associated with intraepithelial lymphocytes in both the gut and the skin. This prompted us to examine the expression of alpha4beta7 on skin-infiltrating lymphocytes in 12 cases of patch/plaque stage cutaneous T cell lymphoma (CTCL) and in 4 cases of spongiotic dermatitis, which also display intraepidermal T cell accumulation. alpha4beta7 was found to be expressed on 64.8+/-7.4% of intraepidermal and 39.1+/-5.0% of intradermal T lymphocytes in CTCL. There was a significant positive correlation (r=0.58) between the degree of epidermotropism and the percentage of intraepidermal T cells expressing alpha4beta7. Similar findings were observed in spongiotic dermatitis, indicating that this result is not unique to malignant T cells. We evaluated staining of T cells in the same specimens for presence of alphaEbeta7 and observed a strong correlation between the expression of both beta7 integrins in each specimen. Staining with antibodies directed against the known ligands of alpha4beta7 was also performed on skin biopsies from CTCL patients. There was significantly increased dermal microvascular endothelial expression of vascular cell adhesion molecule-1 in lesional compared with nonlesional skin, and in nonlesional skin compared with skin of normal control subjects. Dermal and epidermal expression of the CS-1 domain of fibronectin was present but not increased in lesional biopsies compared with nonlesional or normal controls, whereas expression of mucosal addressin cell adhesion molecule-1 was not detectable in any skin biopsy specimens. In summary, alpha4beta7, like alphaEbeta7, is expressed at high levels on epidermotropic T cells and may interact with endothelial cell vascular cell adhesion molecule-1 as part of stepwise recruitment of lymphocytes from the blood to the epidermis.
整合素α4β7与恶性和炎性淋巴细胞向胃肠道黏膜的组织特异性归巢有关，而整合素αEβ7与肠道和皮肤中的上皮内淋巴细胞有关。这促使我们检测12例斑块/斑片期皮肤T细胞淋巴瘤（CTCL）和4例海绵状皮炎患者皮肤浸润淋巴细胞上α4β7的表达，这两种疾病也表现为表皮内T细胞聚集。在CTCL中，发现α4β7在64.8±7.4%的表皮内T淋巴细胞和39.1±5.0%的真皮内T淋巴细胞上表达。表皮趋向性程度与表达α4β7的表皮内T细胞百分比之间存在显著正相关（r = 0.58）。在海绵状皮炎中也观察到类似结果，表明这一结果并非恶性T细胞所特有。我们评估了同一标本中T细胞αEβ7的染色情况，发现每个标本中两种β7整合素的表达之间存在很强的相关性。我们还对CTCL患者的皮肤活检组织进行了针对α4β7已知配体的抗体染色。与非病变皮肤相比，病变皮肤中血管细胞黏附分子-1的真皮微血管内皮表达显著增加，与正常对照皮肤相比，非病变皮肤中该表达也增加。与非病变或正常对照相比，病变活检组织中纤连蛋白CS-1结构域的真皮和表皮表达存在，但未增加，而在任何皮肤活检标本中均未检测到黏膜地址素细胞黏附分子-1的表达。总之，α4β7与αEβ7一样，在表皮趋向性T细胞上高水平表达，并可能与内皮细胞血管细胞黏附分子-1相互作用，作为淋巴细胞从血液逐步募集到表皮的一部分。
