Gupta A K, Baadsgaard O, Ellis C N, Voorhees J J, Cooper K D
Department of Dermatology, University of Michigan Medical Center, Ann Arbor 48109.
Arch Dermatol Res. 1989;281(4):219-26. doi: 10.1007/BF00431054.
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 specimens 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 cells/non-Langerhans CD1-DR+ epidermal cells changing from a mean of 0.82 at baseline to 1.92 at day 14.(ABSTRACT TRUNCATED AT 250 WORDS)
由于环孢素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病情缓解中发挥作用。为了确定CsA对银屑病的早期影响,我们使用双重免疫荧光显微镜对治疗前以及CsA治疗3天、7天和14天后获取的活检标本中的免疫细胞进行定量分析。CsA治疗导致银屑病皮肤中免疫细胞(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。这种作用迅速,包括T细胞、活化T细胞、单核细胞和朗格汉斯细胞(LCs)在内的HLe1 +(人类白细胞抗原-1阳性或骨髓来源)细胞密度在3天内降低了一半以上。尽管皮肤中免疫细胞的总数减少,但治疗后T细胞、朗格汉斯细胞和单核细胞在免疫细胞总数中的比例未发生变化,这反映出各亚型细胞数量的减少比例相同。真皮CD1 + DR +细胞(假定的朗格汉斯细胞)在正常皮肤中不存在,但存在于银屑病皮损皮肤中,在CsA治疗后几乎从乳头真皮中清除。虽然定义为同时表达CD1(T6)和DR分子(CD1 + DR +)的表皮朗格汉斯细胞的绝对数量在CsA治疗后也减少了,但表皮非朗格汉斯CD1 - DR +细胞(巨噬细胞、活化T细胞、DR -角质形成细胞)的减少比例更大,CD1 + DR +朗格汉斯细胞/非朗格汉斯CD1 - DR +表皮细胞的比例从基线时的平均0.82变为第14天时的1.92。(摘要截选至250字)