Etoh K, Tamiya S, Yamaguchi K, Okayama A, Tsubouchi H, Ideta T, Mueller N, Takatsuki K, Matsuoka M
Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Cancer Res. 1997 Nov 1;57(21):4862-7.
Clonal proliferation of human T-lymphotropic virus type I (HTLV-I)-infected cells has been detected by Southern blot analysis and inverse PCR in patients with adult T-cell leukemia, patients with HTLV-I-associated diseases, and even in asymptomatic carriers. Combining inverse PCR with long PCR, we amplified the genomic DNA regions flanking the integration sites of the HTLV-I provirus to detect clones of infected cells. Inverse long PCR revealed that increased virus load was associated with an increase of both the number of cells in each clone and the number of clones. Clonal proliferations were found in both CD4- and CD8-positive cells in a carrier and a patient with HTLV-I-associated neuropathy/tropical spastic paraparesis. These HTLV-I-infected clones persisted over several years in the same carriers, and, moreover, most of the persistent clones were CD4 positive in a HTLV-I carrier. These findings indicate that HTLV-I infection plays an important role in the clonal expansion of lymphocytes and the prolonged survival of CD4-positive cells in vivo. Surviving T-lymphocytes may be susceptible to genetic changes, leading to the onset of leukemia.
通过Southern印迹分析和反向PCR，在成人T细胞白血病患者、HTLV-I相关疾病患者甚至无症状携带者中检测到了人嗜T淋巴细胞病毒I型（HTLV-I）感染细胞的克隆增殖。将反向PCR与长PCR相结合，我们扩增了HTLV-I前病毒整合位点两侧的基因组DNA区域，以检测感染细胞的克隆。反向长PCR显示，病毒载量增加与每个克隆中的细胞数量和克隆数量的增加有关。在一名携带者和一名患有HTLV-I相关神经病变/热带痉挛性截瘫的患者的CD4和CD8阳性细胞中均发现了克隆增殖。这些HTLV-I感染的克隆在同一携带者中持续存在数年，此外，在一名HTLV-I携带者中，大多数持续存在的克隆为CD4阳性。这些发现表明，HTLV-I感染在淋巴细胞的克隆扩增和体内CD4阳性细胞的长期存活中起重要作用。存活的T淋巴细胞可能易发生基因变化，从而导致白血病的发生。
