Wenzel J, Uerlich M, Wörrenkämper E, Freutel S, Bieber T, Tüting T
Department of Dermatology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
Br J Dermatol. 2005 Nov;153(5):1011-5. doi: 10.1111/j.1365-2133.2005.06784.x.
Infiltrating T lymphocytes are considered to play a major pathological role in skin lesions of cutaneous lupus erythematosus (CLE), a cutaneous autoimmune disease of unknown aetiology. Earlier histological studies revealed that the inflammatory infiltrate in CLE skin lesions is predominantly composed of T lymphocytes, with a slight predominance of CD4+ over CD8+ T cells, but failed to explain the development of scarring skin lesions, characteristic for chronic discoid lupus erythematosus (CDLE). Because recent investigations have highlighted the relevance of cytotoxic lymphocytes in autoimmune tissue destruction, we hypothesized that the scarring CDLE lesions might be caused by cytotoxic T lymphocytes.
To analyse skin biopsies of 15 patients with CLE [10 female, five male; localized CDLE (lCDLE), n = 5; disseminated CDLE (dCDLE), n = 5, subacute CLE (SCLE), n = 5] and five control biopsies taken from healthy controls and to characterize the inflammatory infiltrate. Methods We used immunohistochemistry, including staining for the cytotoxic molecule granzyme B, the skin-homing molecule cutaneous lymphocyte antigen (CLA) and the protein MxA, which is specifically induced by type I interferons (IFNs).
We found a strong coexpression of granzyme B and CLA on lesional lymphocytes of patients with scarring lCDLE and dCDLE, which was significantly enhanced when compared with nonscarring SCLE and healthy controls. The increased expression of granzyme B was closely associated with the lesional expression of the type I IFN-induced protein MxA.
Our results provide evidence that type I IFNs and potentially autoreactive cytotoxic lymphocytes targeting adnexal structures are highly associated with scarring lupus erythematosus lesions and might be responsible for their scarring character.
浸润性T淋巴细胞被认为在皮肤红斑狼疮（CLE）的皮肤病变中起主要病理作用，CLE是一种病因不明的皮肤自身免疫性疾病。早期的组织学研究表明，CLE皮肤病变中的炎性浸润主要由T淋巴细胞组成，CD4 + T细胞略多于CD8 + T细胞，但未能解释瘢痕性皮肤病变（慢性盘状红斑狼疮（CDLE）的特征性病变）的发生发展。由于最近的研究强调了细胞毒性淋巴细胞在自身免疫性组织破坏中的相关性，我们推测瘢痕性CDLE病变可能由细胞毒性T淋巴细胞引起。
分析15例CLE患者[10例女性，5例男性；局限性CDLE（lCDLE），n = 5；播散性CDLE（dCDLE），n = 5，亚急性CLE（SCLE），n = 5]的皮肤活检标本以及取自健康对照的5份对照活检标本，并对炎性浸润进行特征分析。方法：我们使用了免疫组织化学方法，包括对细胞毒性分子颗粒酶B、皮肤归巢分子皮肤淋巴细胞抗原（CLA）以及由I型干扰素（IFN）特异性诱导的MxA蛋白进行染色。
我们发现，在瘢痕性lCDLE和dCDLE患者的病变淋巴细胞上，颗粒酶B和CLA强烈共表达，与非瘢痕性SCLE和健康对照相比，这种共表达显著增强。颗粒酶B表达的增加与I型干扰素诱导蛋白Mx A的病变表达密切相关。
我们的结果表明，I型干扰素以及可能靶向附属器结构的自身反应性细胞毒性淋巴细胞与瘢痕性红斑狼疮病变高度相关，可能是其瘢痕形成特征的原因。
