Yamaguchi T, Ohshima K, Karube K, Kawano R, Nakayama J, Suzumiya J, Kikuchi M
Department of Pathology, School of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Br J Dermatol. 2006 May;154(5):904-9. doi: 10.1111/j.1365-2133.2005.07039.x.
Little is known about the mechanisms involved in skin-specific homing in CD30+ cutaneous lymphoproliferative disorders (CLPD). Chemokine/chemokine receptor interactions have been implicated in the homing of lymphoma cells to various tissue sites.
To investigate tissue samples from patients with CD30+ CLPD for the expression of the chemokine receptors CXCR3, CCR4 and CCR3 and their ligands MIG, TARC and RANTES.
Tissue samples from patients with primary cutaneous anaplastic large cell lymphoma (PCALCL, n=12) and lymphomatoid papulosis (LyP, n=13) were studied by immunohistochemistry on paraffin-embedded sections. Immunohistochemical analysis was also performed for CD20 (for B cells), CD45RO and CD3 (for T cells), CD30 and ALK-1. A portion of each skin specimen was stored at -80 degrees C and later examined using monoclonal antibodies against CD2, CD3, CD4, CD5, CD8, CD15, CD19, CD20 and CD30.
CD30+ atypical lymphoid cells were frequently seen in PCALCL, and to a variable degree in LyP. In both disorders there were scattered CD3+ and CD45RO+ atypical lymphoid cells, but CD2, CD5, CD15, CD19, CD20 and ALK-1 showed negative reactivity. In addition, CD4+, but not CD8+, atypical lymphoid cells were occasionally seen in both disorders. CCR3 was expressed by atypical lymphoid cells in 10 of 12 (83%) cases of PCALCL, but in only five of 13 (38%) cases of LyP. CXCR3 was expressed in 11 of 13 (85%) cases of LyP, but in only one of 12 (8%) cases of PCALCL. CCR4 was expressed in 11 of 12 (92%) cases of PCALCL, but in only two of 13 (15%) cases of LyP. RANTES was strongly expressed by lymphoma cells in PCALCL (11 of 12: 92%), but was weak or sporadic in LyP (seven of 13: 54%). TARC showed weak or sporadic reactivity in both LyP and PCALCL, and MIG did not show a distinctive expression pattern in either disorder.
We speculate that CCR3 is associated with the autocrine function in PCALCL, as evidenced by CCR3 coexpression with its ligand RANTES. We also found that LyP cells expressed CXCR3, which might support their migration towards the CXCR3 ligand MIG, which is expressed in stromal cells of the skin.
关于CD30+皮肤淋巴增生性疾病(CLPD)中皮肤特异性归巢所涉及的机制知之甚少。趋化因子/趋化因子受体相互作用与淋巴瘤细胞归巢至各种组织部位有关。
研究CD30+CLPD患者的组织样本中趋化因子受体CXCR3、CCR4和CCR3及其配体MIG、TARC和RANTES的表达情况。
对原发性皮肤间变性大细胞淋巴瘤(PCALCL,n = 12)和淋巴瘤样丘疹病(LyP,n = 13)患者的组织样本进行石蜡包埋切片免疫组织化学研究。还对CD20(用于B细胞)、CD45RO和CD3(用于T细胞)、CD30和ALK-1进行了免疫组织化学分析。每个皮肤标本的一部分保存在-80℃,随后使用抗CD2、CD3、CD4、CD5、CD8、CD15、CD19、CD20和CD30的单克隆抗体进行检测。
在PCALCL中经常可见CD30+非典型淋巴细胞,在LyP中可见程度不一。在这两种疾病中均有散在的CD3+和CD45RO+非典型淋巴细胞,但CD2、CD5、CD15、CD19、CD20和ALK-1呈阴性反应。此外,在这两种疾病中偶尔可见CD4+而非CD8+非典型淋巴细胞。12例PCALCL中的10例(83%)非典型淋巴细胞表达CCR3,但13例LyP中仅5例(38%)表达。13例LyP中的11例(85%)表达CXCR3,但12例PCALCL中仅1例(8%)表达。12例PCALCL中的11例(92%)表达CCR4,但13例LyP中仅2例(15%)表达。RANTES在PCALCL的淋巴瘤细胞中强烈表达(12例中的11例:92%),但在LyP中表达较弱或呈散在分布(13例中的7例:54%)。TARC在LyP和PCALCL中均表现出较弱或散在的反应性,MIG在这两种疾病中均未表现出独特的表达模式。
我们推测CCR3与PCALCL中的自分泌功能相关,CCR3与其配体RANTES共表达证明了这一点。我们还发现LyP细胞表达CXCR3,这可能支持它们向皮肤基质细胞中表达的CXCR3配体MIG迁移。