Foss H D, Anagnostopoulos I, Herbst H, Grebe M, Ziemann K, Hummel M, Stein H
Konsultations- und Referenzzentrum für Lymphknoten und Hämatopathologie, Institute of Pathology, Klinikum Benjamin Franklin, Free University of Berlin, Germany.
Blood. 1995 May 15;85(10):2862-9.
Peripheral T-cell lymphoma of angioimmunoblastic lymph-adenopathy type (AILD-TCL) is histologically characterized by a mixed infiltrate of atypical T cells, B cells including B immunoblasts, and plasma cells, as well as eosinophilic granulocytes accompanied by proliferated high endothelial venules, while, clinically, fever and weight loss are often observed. These morphologic and clinical pecularities are widely believed to reflect abnormal patterns of cytokine expression. To evaluate this hypothesis, 11 lymph nodes with AILD-TCL were studied for the presence of tumor necrosis factor-alpha (TNF), lymphotoxin (LT), interleukin-6 (IL-6), and IL-1 beta transcripts by in situ hybridization (ISH) using [35S]-labeled cytokine-specific RNA probes in seven cases subsequent to immunohistology for cell type characteristic antigens. Expression of all four cytokines was strongly enhanced in AILD-TCL when compared with the control groups of lymphoblastic lymphomas and peripheral T-cell lymphomas, other than AILD-TCL. TNF and LT transcripts were present in atypical T cells and in a variable proportion of B immunoblasts in all AILD-TCL cases, whereas IL-6 and IL-1 beta specific transcripts were mainly found in nonlymphoid cells. To verify a possible cytokine expression by Epstein-Barr virus (EBV)-infected cells, which are frequently present in AILD-TCL, the detection of EBV-encoded nuclear RNAs (EBER) was combined with ISH for cytokine transcripts. It became evident that expression of LT and TNF by EBV-infected cells was largely restricted to B immunoblasts, which were only infrequently present in most AILD-TCL cases, whereas the expression of IL-6 was very rare, and IL-1 beta was not found in EBV-infected cells. These data suggest that expression of TNF and LT genes may contribute to the characteristic histologic and clinical features of AILD-TCL and that cytokine expression by EBV-infected cells does not, in most cases, contribute significantly to the overall cytokine expression. Because it has been shown that LT is an autocrine growth factor for EBV-infected B cells, expression of this cytokine could contribute to the proliferation of EBV-infected B cells in AILD-TCL and, in the setting of immunosuppression, may ultimately play a role in the development of B-immunoblastic lymphomas.
血管免疫母细胞性淋巴结病样外周T细胞淋巴瘤（AILD-TCL）的组织学特征为非典型T细胞、包括B免疫母细胞在内的B细胞和浆细胞的混合浸润，以及伴有高内皮小静脉增生的嗜酸性粒细胞，而在临床上，常观察到发热和体重减轻。人们普遍认为这些形态学和临床特征反映了细胞因子表达的异常模式。为了评估这一假说，我们对11例AILD-TCL淋巴结进行了研究，在7例病例中，在对细胞类型特征性抗原进行免疫组织化学检测之后，使用[35S]标记的细胞因子特异性RNA探针，通过原位杂交（ISH）检测肿瘤坏死因子-α（TNF）、淋巴毒素（LT）、白细胞介素-6（IL-6）和IL-1β转录本。与淋巴母细胞淋巴瘤和除AILD-TCL之外的外周T细胞淋巴瘤对照组相比，AILD-TCL中所有四种细胞因子的表达均显著增强。在所有AILD-TCL病例中，TNF和LT转录本存在于非典型T细胞和不同比例的B免疫母细胞中，而IL-6和IL-1β特异性转录本主要在非淋巴细胞中发现。为了验证爱泼斯坦-巴尔病毒（EBV）感染细胞（AILD-TCL中经常存在）可能的细胞因子表达，将EBV编码的核RNA（EBER）的检测与细胞因子转录本的ISH相结合。很明显，EBV感染细胞中LT和TNF的表达主要局限于B免疫母细胞，而在大多数AILD-TCL病例中B免疫母细胞很少出现，而IL-6的表达非常罕见，在EBV感染细胞中未发现IL-1β。这些数据表明，TNF和LT基因的表达可能有助于AILD-TCL的特征性组织学和临床特征，并且在大多数情况下，EBV感染细胞的细胞因子表达对整体细胞因子表达的贡献不大。因为已经表明LT是EBV感染B细胞的自分泌生长因子，这种细胞因子的表达可能有助于AILD-TCL中EBV感染B细胞的增殖，并且在免疫抑制的情况下，最终可能在B免疫母细胞淋巴瘤的发生中起作用。
