Nickoloff B J, Nestle F O, Zheng X G, Turka L A
Department of Pathology, University of Michigan Medical School, Ann Arbor.
Blood. 1994 May 1;83(9):2580-6.
The activation of T cells requires two distinct signals. One signal involves interaction of the antigen-specific T-cell receptor with major histocompatibility complex molecules plus antigenic peptide; a second signal, which is antigen nonspecific, is the interaction of CD28 with its natural ligands B7-1 and B7-2/B70. CD28 is expressed on 80% of T cells, is upregulated after activation, and binds to B7 gene-family members, found on antigen-presenting cells. Because of our interest in the immunologic basis of benign and malignant T-cell-mediated disorders of the skin, we investigated the cellular distribution of CD28 and B7 family members in lesions of psoriasis and mycosis fungoides. By immunostaining cryostat sections of skin, CD28 was found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. Surprisingly, B7-1 was also found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. B7-1 expression was confirmed on CD3+ T lymphocytes using flow cytometry of single cell suspensions of fresh, unfixed psoriatic lesional tissue. To exclude the possibility that this result was caused by a second reagent contaminating the monoclonal antibody (MoAb) preparation, two different lots were used, and the MoAb was absorbed onto Chinese hamster ovary (CHO) transfectants expressing B7-1, or vector-only transfected CHO cells. These procedures confirmed that a B7-1-like epitope was being recognized on psoriatic lesional T cells. In contrast to B7-1 expression on lymphocytes, B7-3, as defined by anti-BB-1 MoAb reactivity, was found primarily on epidermal keratinocytes in both skin diseases and was not found on T cells. These results indicate that within two common skin disorders, lesional T cells accumulate in the dermis and epidermis, which express B7-1. Such expression may permit self-costimulation involving the CD28-mediated activation pathway, and thereby contribute to the ongoing T-cell proliferation present in these chronic, benign, and malignant skin diseases.
T细胞的激活需要两种不同的信号。一种信号涉及抗原特异性T细胞受体与主要组织相容性复合体分子加上抗原肽的相互作用；第二种信号是非抗原特异性的，是CD28与其天然配体B7-1和B7-2/B70的相互作用。CD28在80%的T细胞上表达，激活后上调，并与抗原呈递细胞上发现的B7基因家族成员结合。由于我们对皮肤良性和恶性T细胞介导疾病的免疫基础感兴趣，我们研究了银屑病和蕈样肉芽肿病变中CD28和B7家族成员的细胞分布。通过对皮肤冰冻切片进行免疫染色，发现两种皮肤病的表皮和真皮中的几乎所有淋巴细胞均表达CD28。令人惊讶的是，两种皮肤病的表皮和真皮中的几乎所有淋巴细胞也都表达B7-1。使用新鲜、未固定的银屑病病变组织单细胞悬液进行流式细胞术，在CD3+T淋巴细胞上证实了B7-1的表达。为排除该结果是由污染单克隆抗体（MoAb）制剂的第二种试剂所致的可能性，使用了两个不同批次的产品，并将该MoAb吸附到表达B7-1的中国仓鼠卵巢（CHO）转染细胞或仅转染载体的CHO细胞上。这些程序证实了在银屑病病变T细胞上识别出了类似B7-1的表位。与淋巴细胞上的B7-1表达相反，由抗BB-1 MoAb反应性定义的B7-3主要在两种皮肤病的表皮角质形成细胞上发现，而在T细胞上未发现。这些结果表明，在两种常见的皮肤病中，病变T细胞在表达B7-1的真皮和表皮中积聚。这种表达可能允许涉及CD28介导的激活途径的自身共刺激，从而促成这些慢性、良性和恶性皮肤病中持续存在的T细胞增殖。
