Simon J C, Dietrich A, Mielke V, Wuttig C, Vanscheidt W, Linsley P S, Schöpf E, Sterry W
Department of Dermatology, University of Freiburg, Germany.
J Invest Dermatol. 1994 Oct;103(4):539-43. doi: 10.1111/1523-1747.ep12395743.
Interactions of CD28 (on T cells) with its recently identified ligand B7/BB1 (on antigen-presenting cells) have been shown to activate T cells via a major histocompatibility complex/Ag-independent "alternative" pathway, leading to an amplification of T-cell-mediated immune responses. The in vivo relevance of these molecules for cutaneous immunity is presently unknown. These findings prompted us to study the expression of B7/BB1 and CD28 in normal human skin and in selected T-cell-mediated inflammatory skin diseases. Biopsies were obtained from lesional skin of patients with allergic contact dermatitis, lichen planus, and, as control, from basal cell carcinoma and from healthy controls. Serial cryostat sections were stained with a panel of MoAbs directed against CD28, B7/BB1, CD3, CD1a, and KiM8 using immunohistochemistry (ABC technique). CD28 expression was observed in the majority of dermal and epidermal CD3+ T cells in contact dermatitis and lichen planus. In normal skin and basal cell carcinoma, CD28 was expressed only occasionally by perivascular T cells. In allergic contact dermatitis and lichen planus, B7/BB1-expression was found on dermal dendritic cells, on dermal macrophages, on Langerhans cells, focally on keratinocytes, and occasionally on dermal T cells. No B7/BB1 immunoreactivity was detected in normal skin and basal cell carcinoma. These findings indicate that T-cell-mediated skin diseases are accompanied by an influx of CD28+ T cells and an upregulation of B7/BB1 on cutaneous antigen-presenting cells, keratinocytes, and on some T cells. We speculate that "alternative" T cell-activation via the B7/CD28 pathway may contribute to the pathogenesis of these skin diseases.
已证实,(T细胞上的)CD28与其最近发现的配体B7/BB1(抗原呈递细胞上的)相互作用,可通过主要组织相容性复合体/抗原非依赖性“替代”途径激活T细胞,从而导致T细胞介导的免疫反应增强。目前尚不清楚这些分子在皮肤免疫中的体内相关性。这些发现促使我们研究B7/BB1和CD28在正常人类皮肤以及某些T细胞介导的炎症性皮肤病中的表达情况。从过敏性接触性皮炎、扁平苔藓患者的皮损处取材活检,作为对照,还从基底细胞癌患者和健康对照者处取材。连续冰冻切片采用免疫组织化学(ABC技术),用一组针对CD28、B7/BB1、CD3、CD1a和KiM8的单克隆抗体进行染色。在接触性皮炎和扁平苔藓的大多数真皮和表皮CD3+T细胞中观察到CD28表达。在正常皮肤和基底细胞癌中,仅偶尔在血管周围T细胞中检测到CD28表达。在过敏性接触性皮炎和扁平苔藓中,在真皮树突状细胞、真皮巨噬细胞、朗格汉斯细胞上发现B7/BB1表达,在角质形成细胞中有局灶性表达,在真皮T细胞中偶尔也有表达。在正常皮肤和基底细胞癌中未检测到B7/BB1免疫反应性。这些发现表明,T细胞介导的皮肤疾病伴随着CD28+T细胞的流入以及皮肤抗原呈递细胞、角质形成细胞和一些T细胞上B7/BB1的上调。我们推测,通过B7/CD28途径的“替代”T细胞激活可能参与了这些皮肤病的发病机制。