Serrano D, Ghiotto F, Roncella S, Airoldi I, Cutrona G, Truini M, Burgio V L, Baroni C D, Ferrarini M, Pistoia V
Service of Clinical Immunology, National Institute for Cancer Research, Rome, Italy.
Haematologica. 1997 Sep-Oct;82(5):542-9.
The lymph nodes involved in classic Hodgkin's disease (HD), i.e. mixed cellularity (MC) and nodular sclerosis (NS) subtypes, usually contain few (1-2%) Reed-Sternberg (RS) cells scattered in a background of lymphocytes, eosinophils, plasma cells and neutrophils. CD4+ T-lymphocytes are increased in number, express activation markers and cluster around RS cells. The presence of eosinophilia in most HD patients and the presence of hyper-IgE in a subset of them may suggest that activated lymph node T cells release large amounts of IL5 and IL4, respectively.
The expression of four T-cell-associated cytokine genes, i.e. interleukin (IL)2, IL4, IL5 and interferon (IFN)-gamma, in frozen sections of 14 HD (7 MC, 7 NS) and 10 reactive lymph nodes was investigated by qualitative and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). T-cell clones were also raised from purified CD4+ lymphocytes of one HD lymph node and one reactive lymph node and tested for IL2, IL4, IL5 and IFN-gamma secretion in culture supernatants by immunoassays.
The transcripts of all the cytokine genes were detected in every lymph node irrespective of the HD or reactive nature. HD or reactive lymph node-derived CD4+ T-cell clones released the four cytokines according to a predominant T-helper (Th)0-type pattern. In more than half of the lymph nodes of either HD or reactive nature, there was a predominance of IL4 over IFN-gamma mRNA production (Th2-type pattern). In the remaining HD or reactive lymphadenopathies, either a balanced IL4/IFN-gamma mRNA ratio (Th0-type pattern) or a predominance of IFN-gamma over IL4 mRNA expression (Th1-type pattern) was observed.
The overall pattern of cytokine gene expression in classic HD is similar to that detected in reactive lymph nodes. Further studies are needed to determine whether differences in the absolute concentrations of cytokines released in HD versus reactive lymph nodes and the long-standing course of HD versus the self-limiting nature of reactive adenopathies may explain certain peculiar features of HD, such as eosinophilia, for example.
经典型霍奇金淋巴瘤（HD）累及的淋巴结，即混合细胞型（MC）和结节硬化型（NS）亚型，通常含有少量（1% - 2%）散在于淋巴细胞、嗜酸性粒细胞、浆细胞和中性粒细胞背景中的里德 - 斯腾伯格（RS）细胞。CD4 + T淋巴细胞数量增加，表达活化标志物并聚集在RS细胞周围。大多数HD患者存在嗜酸性粒细胞增多，其中一部分患者存在高IgE血症，这可能提示活化的淋巴结T细胞分别释放大量的IL5和IL4。
采用定性和定量逆转录聚合酶链反应（RT - PCR）研究14例HD（7例MC，7例NS）和10例反应性淋巴结冰冻切片中四种T细胞相关细胞因子基因，即白细胞介素（IL）2、IL4、IL5和干扰素（IFN）-γ的表达。还从一个HD淋巴结和一个反应性淋巴结的纯化CD4 +淋巴细胞中培养T细胞克隆，并通过免疫测定检测培养上清液中IL2、IL4、IL5和IFN -γ的分泌情况。
无论淋巴结是HD还是反应性的，所有细胞因子基因的转录本均能检测到。HD或反应性淋巴结来源的CD4 + T细胞克隆按照主要的辅助性T细胞（Th）0型模式释放这四种细胞因子。在超过一半的HD或反应性淋巴结中，IL4的mRNA产量高于IFN -γ（Th2型模式）。在其余的HD或反应性淋巴结病中，观察到IL4/IFN -γ mRNA比例平衡（Th0型模式）或IFN -γ的mRNA表达高于IL4（Th1型模式）。
经典型HD中细胞因子基因表达的总体模式与反应性淋巴结中检测到的模式相似。需要进一步研究以确定HD与反应性淋巴结中释放的细胞因子绝对浓度的差异以及HD的长期病程与反应性淋巴结病的自限性本质是否可以解释HD的某些特殊特征，例如嗜酸性粒细胞增多。
