Lusso P, Markham P D, Tschachler E, di Marzo Veronese F, Salahuddin S Z, Ablashi D V, Pahwa S, Krohn K, Gallo R C
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland 20892.
J Exp Med. 1988 May 1;167(5):1659-70. doi: 10.1084/jem.167.5.1659.
We investigated the cellular tropism of human B-lymphotropic virus (HBLV) (also designated Human Herpesvirus-6) in vitro by infecting fresh MN cells from normal human adult peripheral blood, umbilical cord blood, bone marrow, tonsil, and thymus. Cultures from all the sources examined contained infectable cells, as shown by the appearance of characteristic enlarged, round-shaped, short-lived cells expressing HBLV-specific markers. Detailed immunological analysis demonstrated that the vast majority of these cells expressed T cell-associated antigens (i.e., CD7, CD5, CD2, CD4, and to a lesser extent, CD8). The CD3 antigen and the TCR-alpha/beta heterodimer were not detectable on the surface membrane, but were identified within the cytoplasm of HBLV-infected cells, by both immunofluorescence and radioimmunoprecipitation assay. A proportion of the HBLV-infected cell population also expressed the CD15 and class II MHC DR antigens. By means of immunoselection procedures it was possible to show that a consistent proportion of HBLV-infectable cells were contained within the CD3-depleted immature T cell population, while the depletion of CD2+ cells completely abrogated the infectability of the cultures. Northern blot analysis confirmed the T cell origin of HBLV-infected cells, demonstrating the expression of full size TCR-alpha and -beta chain mRNA. In addition to fresh T cells, HBLV was able to infect normal T lymphocytes expanded in vitro with IL-2 for greater than 30 d. These results indicate that HBLV is selectively T cell tropic in the course of the in vitro infection of normal mononuclear cells and may therefore be directly involved in the pathogenesis of T cell related hematological disorders. In particular, in light of the cytopathic effect exerted in vitro on CD4+ T lymphocytes, a possible role of HBLV in immune deficiency conditions should be considered.
我们通过用人类嗜B淋巴细胞病毒（HBLV）（也称为人类疱疹病毒6型）感染来自正常成人外周血、脐带血、骨髓、扁桃体和胸腺的新鲜MN细胞，在体外研究了该病毒的细胞嗜性。所有检测来源的培养物中均含有可感染细胞，表现为出现表达HBLV特异性标志物的特征性肿大、圆形、寿命短暂的细胞。详细的免疫学分析表明，这些细胞中的绝大多数表达T细胞相关抗原（即CD7、CD5、CD2、CD4，以及程度较轻的CD8）。通过免疫荧光和放射免疫沉淀分析，在感染HBLV的细胞表面膜上未检测到CD3抗原和TCR-α/β异二聚体，但在其细胞质中检测到了它们。一部分感染HBLV的细胞群体还表达CD15和II类MHC DR抗原。通过免疫选择程序可以表明，在CD3缺失的未成熟T细胞群体中始终含有一定比例的可被HBLV感染的细胞，而CD2+细胞的缺失则完全消除了培养物的感染性。Northern印迹分析证实了感染HBLV的细胞来源于T细胞，证明了全长TCR-α和-β链mRNA的表达。除了新鲜T细胞外，HBLV还能够感染用IL-2体外扩增超过30天的正常T淋巴细胞。这些结果表明，在正常单核细胞的体外感染过程中，HBLV具有选择性的T细胞嗜性，因此可能直接参与T细胞相关血液系统疾病的发病机制。特别是，鉴于其在体外对CD4+ T淋巴细胞产生的细胞病变效应，应考虑HBLV在免疫缺陷疾病中的可能作用。
