LYMPHOCYTES AND MACROPHAGES OF THE EPIDERMIS AND DERMIS IN LESIONAL PSORIATIC SKIN, BUT NOT EPIDERMAL LANGERHANS CELLS, ARE DEPLETED BY TREATMENT WITH CYCLOSPORINE-A

LYMPHOCYTES AND MACROPHAGES OF THE EPIDERMIS AND DERMIS IN LESIONAL PSORIATIC SKIN, BUT NOT EPIDERMAL LANGERHANS CELLS, ARE DEPLETED BY TREATMENT WITH CYCLOSPORINE-A
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DOI:
10.1007/bf00431054
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发表时间:
1989-01-01
影响因子:
3
通讯作者:
COOPER, KD
COOPER, KD
中科院分区:
医学3区
文献类型:
--
作者:
GUPTA, AK;BAADSGAARD, O;COOPER, KD

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由于环孢菌素A(CsA)是一种免疫抑制剂,其对银屑病的有益作用表明免疫细胞可能在银屑病的发病机制和消退中发挥作用。为了确定CsA在银屑病中的早期作用,我们使用双重免疫荧光显微镜对治疗前和CsA治疗3、7和14天后获得的活检组织中的免疫细胞进行定量。CsA治疗导致银屑病皮肤内所含免疫细胞(包括T细胞、单核细胞/巨噬细胞和抗原呈递细胞)的绝对数量显著减少。作用迅速,在3天内发生超过一半的HLe 1+(人类白细胞抗原-1阳性或骨髓衍生)细胞密度降低,包括T细胞、活化T细胞、单核细胞和朗格汉斯细胞(LC)。尽管皮肤中免疫细胞的数量总体减少,但T细胞、朗格汉斯细胞和单核细胞相对于免疫细胞总数的比例在治疗中没有变化,反映出每种亚型的损失比例相同。真皮CD 1 +DR+细胞(推定的朗格汉斯细胞),这是没有发现在正常皮肤,但存在于皮损银屑病皮肤,几乎清除后CsA治疗的乳头状真皮。虽然表皮朗格汉斯细胞(定义为表达CD 1(T6)和DR分子(CD 1 +DR+)的细胞)的绝对数量也在CsA后减少,但表皮非朗格汉斯CD 1-DR+细胞(巨噬细胞、活化的T细胞、DR-角质形成细胞)表现出成比例的更大降低,CD 1 +DR+朗格汉斯细胞/非朗格汉斯CD 1-DR+表皮细胞的比率从基线时的平均值0.82变化至第14天的1.92。因此,在治疗过程的早期,CsA似乎在清除CD 1-DR+细胞方面是有效的,同时在表皮中留下相对完整的LC。
Since cyclosporin A (CsA) is an immunosuppressive agent, its beneficial effect in psoriasis suggests that immune cells may play a role in the pathogenesis and resolution of psoriasis. To determine early effects of CsA in psoriasis, we quantitated immune cells using double immunofluorescence microscopy on biopsy speciments obtained prior to therapy and after 3,7, and 14 days of CsA therapy. CsA therapy resulted in significant reductions in the absolute number of immune cells (including T cells, monocytes/ macrophages, and antigen presenting cells) contained within psoriatic skin. The effect was rapid, with over one-half of the reduction in the density of HLe1+ (human leukocyte antigen-1 positive or bone marrow derived) cells, including T cells, activated T cells, monocytes, and Langerhans cells (LCs), occurring within 3 days. Despite the overall reduction in the numbers of immunocytes in the skin, the proportion of T cells, Langerhans cells, and monocytes in relation to the total number of immune cells was unchanged with therapy, reflecting equally proportional losses of each subtype. Dermal CD1+DR+ cells (putative Langerhans cells), which are not found in normal skin but are present in lesional psoriasis skin, were virtually cleared from the papillary dermis after CsA therapy. Although absolute numbers of epidermal Langerhans cells, defined as cells expressing both CD1 (T6) and DR molecules (CD1+DR+), were also reduced after CsA, epidermal non-Langerhans CD1-DR+ cells (macrophages, activated T cells, DR- keratinocytes) demonstrated a proportionally greater decrease, with the ratio of CD1+DR+ Langerhans cell/non-Langerhans CD1-DR+ epidermal cells changing from a mean of 0.82 at baseline to 1.92 at day 14. Thus, early in the course of therapy, CsA appears to be effective at clearing CD1-DR+ cells while leaving LC relatively intact in the epidermis.