Gabrilovich D I, Roberts M S, Harvey J J, Botcherby M, Bedford P A, Knight S C
Antigen Presentation Group, Clinical Research Centre, Harrow, GB.
Eur J Immunol. 1993 Nov;23(11):2932-8. doi: 10.1002/eji.1830231131.
In asymptomatic human immunodeficiency virus-1 infection T cells respond normally to allogeneic dendritic cells (DC), but DC show reduced stimulatory capacity. By contrast in HTLV-1 infection no significant changes in allogeneic stimulation were seen but DC-stimulated activity of autologous T cells. In seeking animal models relevant to these diseases the effects of two murine leukemia retroviruses, Rauscher leukemia virus (RLV) and Moloney leukemia virus (MLV) on the function of dendritic cells and T cells in a primary mixed leucocyte reaction have been tested. Treatment by RLV in vitro suppressed the ability of DC to stimulate allogeneic T cells from healthy animals. MLV at the same concentration did not significantly affect the ability of DC to stimulate allogeneic T cells, but provoked considerable enhancement of the low level stimulation by DC in the syngeneic system. Similar results were obtained following in vivo exposure to viruses. Two pieces of evidence suggested that these effects were due to impairment of DC function and were not operating through infection of T cells. Firstly, exposure of T cells directly to virus in vitro and in vivo before stimulation with untreated allogeneic DC caused no significant alteration in T cell activity. Secondly, the impact of murine leukemia virus on DC function was not abrogated when infected DC were added to normal T cells and cultured in the presence of zidovudine. Treatment of DC by RLV caused a decrease of cluster formation with allogeneic T cells. No statistically significant influence of MLV was observed on cluster formation after 3-h of incubation in the allogeneic system. However, after 18-h incubation MLV-treated DC formed fewer clusters with T cells than untreated DC. At the same time a stimulatory effect of MLV on DC cluster formation with syngeneic T cells was found. Considerable decrease was found in major histocompatibility complex class II antigen and LFA-1 receptor expression on the DC surface in mice infected by RLV. MLV induced no significant changes. These mouse retroviruses can therefore cause changes in DC function similar to those already reported using human retroviruses and may provide models for studying their effects.
在无症状人类免疫缺陷病毒1型感染中，T细胞对同种异体树突状细胞（DC）反应正常，但DC的刺激能力降低。相比之下，在人类嗜T淋巴细胞病毒1型感染中，同种异体刺激未见明显变化，但DC刺激的自体T细胞活性有所改变。在寻找与这些疾病相关的动物模型时，测试了两种鼠白血病逆转录病毒，劳舍尔白血病病毒（RLV）和莫洛尼白血病病毒（MLV）对初次混合淋巴细胞反应中树突状细胞和T细胞功能的影响。体外RLV处理抑制了DC刺激健康动物同种异体T细胞的能力。相同浓度的MLV对DC刺激同种异体T细胞的能力无显著影响，但在同基因系统中显著增强了DC的低水平刺激。体内接触病毒后也得到了类似结果。两条证据表明这些效应是由于DC功能受损，而非通过感染T细胞起作用。首先，在用未处理的同种异体DC刺激之前，T细胞在体外和体内直接接触病毒，T细胞活性未发生显著改变。其次，当将感染的DC加入正常T细胞并在齐多夫定存在下培养时，鼠白血病病毒对DC功能的影响并未消除。RLV处理DC导致与同种异体T细胞形成的簇减少。在同种异体系统中孵育3小时后，未观察到MLV对簇形成有统计学显著影响。然而，孵育18小时后，经MLV处理的DC与T细胞形成的簇比未处理的DC少。同时发现MLV对DC与同基因T细胞形成簇有刺激作用。感染RLV的小鼠DC表面主要组织相容性复合体II类抗原和淋巴细胞功能相关抗原-1受体表达显著降低。MLV未诱导显著变化。因此，这些小鼠逆转录病毒可引起DC功能变化，类似于使用人类逆转录病毒已报道的变化，可能为研究其作用提供模型。
