Hein A, Czub S, Xiao L X, Schwender S, Dörries R, Czub M
Institut für Virologie und Immunbiologie, Würzburg, Germany.
Virology. 1995 Aug 20;211(2):408-17. doi: 10.1006/viro.1995.1423.
In a rat model, we have investigated the effects of adoptively transferred virus-specific immune cells on an established retroviral infection of various organs. The experimental design required inoculation of neonatal Fisher rats with a molecular clone of Friend murine leukemia virus (F-MuLV; FB29) which resulted in virus-specific immunotolerance, while infection of adult rats lead to a virus-specific humoral and cellular immune response. Adoptive transfer of virus-specific immune cells from immunized to immunotolerant (i.e., neonatally inoculated) rats was performed at around 15 days postpartum, a time when retroviral titers had already reached high levels in serum, spleen, thymus, and central nervous system (CNS). Seven days post-transfer (dpt), virus titers began to decline by 3-5 logs first in sera and at around 11-15 dpt, in spleens and thymi. Approximately 19 days post-transfer viral titers increased again. In the CNS, viral titers appeared not to change after adoptive transfer, although we observed an influx of activated T-cells and natural killer cells (NK-cells), but not of B-cells, into the CNS as well as an upregulation of major histocompatibility complex class I and II molecules between 8 and 21 dpt on both microglia and other brain cells. From these data we conclude that MuLV-infected cells of lymphoid organs can be eliminated by an antiviral immune response. In the CNS, however, most virus-infected cells escaped an immunological attack in spite of the presence of T- and NK-cells and may thus function as a reservoir for MuLVs.
在大鼠模型中，我们研究了过继转移病毒特异性免疫细胞对已建立的各种器官逆转录病毒感染的影响。实验设计要求用弗氏小鼠白血病病毒（F-MuLV；FB29）的分子克隆接种新生Fisher大鼠，这会导致病毒特异性免疫耐受，而成年大鼠感染则会引发病毒特异性体液免疫和细胞免疫反应。在产后约15天，将病毒特异性免疫细胞从免疫大鼠过继转移到免疫耐受（即新生期接种）大鼠，此时逆转录病毒滴度在血清、脾脏、胸腺和中枢神经系统（CNS）中已达到高水平。转移后7天（dpt），病毒滴度首先在血清中开始下降3 - 5个对数，在大约11 - 15 dpt时，脾脏和胸腺中的病毒滴度也开始下降。转移后约19天，病毒滴度再次升高。在中枢神经系统中，过继转移后病毒滴度似乎没有变化，尽管我们观察到在8至21 dpt期间，活化的T细胞和自然杀伤细胞（NK细胞）而非B细胞流入中枢神经系统，并且小胶质细胞和其他脑细胞上的主要组织相容性复合体I类和II类分子上调。从这些数据我们得出结论，淋巴器官中感染MuLV的细胞可通过抗病毒免疫反应被清除。然而，在中枢神经系统中，尽管存在T细胞和NK细胞，大多数病毒感染细胞仍逃脱了免疫攻击，因此可能作为MuLV的储存库。
