Höllsberg P, Wucherpfennig K W, Ausubel L J, Calvo V, Bierer B E, Hafler D A
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115.
J Immunol. 1992 May 15;148(10):3256-63.
Mononuclear cells from subjects infected with human T lymphotrophic virus type I (HTLV-I) display a unique ability to proliferate in vitro in the absence of mitogens or exogenous growth factors. Subjects who have developed an HTLV-I-associated myelopathy (HAM) show an even higher degree of spontaneous proliferation concomitant with transcription of the HTLV-I provirus. The mechanism underlying HTLV-I-induced T cell activation was investigated by characterizing a series of HTLV-I-infected T cell clones generated from the blood of subjects with HAM. Approximately 15% of the T cell clones generated were HTLV-I infected as determined by polymerase chain reaction and Southern blotting. Infected T cell clones displayed altered growth kinetics as they continued to incorporate tritiated thymidine 7 to 14 days after stimulation, a time when noninfected T cell clones had returned to a resting state. This was not due to transformation as all the T cell clones required periodic restimulation with mitogens and feeder cells for continued growth. Although HTLV-I-infected T cell clones showed increased expression of the IL-2 receptor p55 chain, the spontaneous clonal proliferation was not inhibited by anti-IL-2 receptor mAb. Moreover, the spontaneous clonal proliferation was insensitive to cyclosporin A and FK 506 while being highly sensitive to rapamycin, which is known to inhibit IL-2-mediated signaling. Together these results demonstrate that IL-2 is not required for the HTLV-I-induced spontaneous clonal proliferation and further suggest that HTLV-I may induce signaling pathways replacing an IL-2 receptor signal proximal to the site of action of rapamycin.
来自感染I型人类嗜T淋巴细胞病毒（HTLV-I）的受试者的单核细胞，在没有丝裂原或外源性生长因子的情况下，表现出独特的体外增殖能力。已发展为HTLV-I相关脊髓病（HAM）的受试者表现出更高程度的自发增殖，并伴有HTLV-I前病毒的转录。通过对一系列从HAM受试者血液中产生的HTLV-I感染的T细胞克隆进行表征，研究了HTLV-I诱导T细胞活化的机制。通过聚合酶链反应和Southern印迹法测定，所产生的T细胞克隆中约15%被HTLV-I感染。感染的T细胞克隆显示出生长动力学改变，因为在刺激后7至14天它们继续掺入氚标记的胸腺嘧啶核苷，而此时未感染的T细胞克隆已恢复到静止状态。这不是由于转化，因为所有T细胞克隆都需要用丝裂原和饲养细胞进行定期再刺激以持续生长。尽管HTLV-I感染的T细胞克隆显示出IL-2受体p55链表达增加，但抗IL-2受体单克隆抗体并未抑制自发的克隆增殖。此外，自发的克隆增殖对环孢菌素A和FK 506不敏感，而对已知抑制IL-2介导信号传导的雷帕霉素高度敏感。这些结果共同表明，HTLV-I诱导的自发克隆增殖不需要IL-2，并且进一步表明HTLV-I可能诱导信号通路，取代雷帕霉素作用位点近端的IL-2受体信号。
