Ueda Satomi, Maeda Yasuhiro, Yamaguchi Terufumi, Hanamoto Hitoshi, Hijikata Yasuki, Tanaka Miyako, Takai Shunsuke, Hirase Chikara, Morita Yasuyoshi, Kanamaru Akihisa
Division of Hematology, Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan.
Hematology. 2008 Jun;13(3):154-62. doi: 10.1179/102453308X316130.
The involvement of adult T-cell leukemia (ATL) cells in organs such as the skin and lymph nodes is observed in about 50% of cases of ATL. Epstein-Barr virus (EBV) infection has often been observed in the clinical course of ATL. In this study, we established two B-cell lines from peripheral blood of patients with ATL. EBV DNA, proviral DNA for HTLV-1 and Tax mRNA were detected in both lines. As part of the characterization of these cells, an enhanced expression of intercellular adhesion molecule-1 (ICAM-1) (CD54) or ICAM-3 (ICAM-3) (CD50), lymphocyte function-1 (LFA-1) (CD11a/CD18), and Mac-1 (CD11b/CD18) was observed. To investigate the role of the interaction of these viruses, we transfected EBV and/or HTLV-1 into a healthy donor's lymphocytes, an EBV-infected B cell line, Raji, and a HTLV-1 negative T-cell line, Jurkat. Enhanced expression of adhesion molecules was also observed in double transfectants (EBV and HTLV-1). In the clinical course of ATL, LMP-1, EBNA-2, CD50 and CD54 were detected in lymph nodes and skin specimens by immunohistochemical staining. Furthermore, high levels of interleukin-4 (IL-4) were detected in these cell lines and transfectants. The results indicated that coinfection with HTLV-1 and EBV may induce aggressive organ involvement through the enhanced expression of adhesion molecules via IL-4 signaling. A new mechanism of ATL involvement is discussed.
约50%的成人T细胞白血病(ATL)病例中可观察到ATL细胞累及皮肤和淋巴结等器官。在ATL的临床病程中常观察到爱泼斯坦-巴尔病毒(EBV)感染。在本研究中,我们从ATL患者外周血中建立了两个B细胞系。在这两个细胞系中均检测到EBV DNA、HTLV-1前病毒DNA和Tax mRNA。作为这些细胞特性的一部分,观察到细胞间黏附分子-1(ICAM-1)(CD54)或ICAM-3(CD50)、淋巴细胞功能相关抗原-1(LFA-1)(CD11a/CD18)以及巨噬细胞抗原-1(Mac-1)(CD11b/CD18)表达增强。为研究这些病毒相互作用的作用,我们将EBV和/或HTLV-1转染至健康供体淋巴细胞、EBV感染的B细胞系Raji以及HTLV-1阴性T细胞系Jurkat。在双重转染细胞(EBV和HTLV-1)中也观察到黏附分子表达增强。在ATL临床病程中,通过免疫组织化学染色在淋巴结和皮肤标本中检测到LMP-1、EBNA-2、CD50和CD54。此外,在这些细胞系和转染细胞中检测到高水平的白细胞介素-4(IL-4)。结果表明,HTLV-1和EBV共同感染可能通过IL-4信号通路增强黏附分子表达,从而诱导侵袭性器官累及。本文讨论了ATL累及的一种新机制。