Gabrilovich D I, Patterson S, Timofeev A V, Harvey J J, Knight S C
Antigen Presentation Group, Imperial College of Science, Technology, and Medicine, Middlesex, United Kingdom.
Clin Immunol Immunopathol. 1996 Aug;80(2):139-46. doi: 10.1006/clin.1996.0107.
Dendritic cells (DC) from mice infected with the murine retrovirus Rauscher leukaemia virus (RLV) are poor stimulators of allogeneic and syngeneic T cells and express lower, but still significant, levels of MHC class II. In this paper we further investigated the mechanism of the dysfunction of DC. DC from infected animals did not cause anergy of T cells during coculture for 3 or 6 days. They did not release a substantial amount of soluble factors which could suppress T cell responses. The low T cell responses on stimulation using RLV-infected DC could be overcome by the addition of control DC. Pretreatment of these control DC with monoclonal antibody against MHC class II molecules completely blocked their ability to restore stimulation of T cells in the presence of infected DC. However, antibody against MHC class I or mismatched MHC class II molecules did not prevent restoration of function. The reduced labeling of surface MHC class II molecules previously reported was shown to reflect a loss in total class II molecules within the cells; MHC class I levels were unaltered by exposure to the virus. In DC from RLV-infected mice biosynthesis of MHC class II was decreased by around 50% at the transcriptional level in comparison with beta-actin. Thus, the down-regulation of surface class II molecules observed in DC following RLV infection is a consequence of a specific block in its biosynthesis and the failure of DC to stimulate T cells may be a direct consequence of the reduced class II levels. Since reduced stimulation by DC is also seen in HIV-1 infection in humans we speculate that a similar mechanism might operate in retroviral infection in man.
感染鼠逆转录病毒劳舍尔白血病病毒（RLV）的小鼠树突状细胞（DC）对同种异体和同基因T细胞的刺激能力较差，且主要组织相容性复合体II类（MHC II）的表达水平较低，但仍具有显著性。在本文中，我们进一步研究了DC功能障碍的机制。来自受感染动物的DC在共培养3天或6天期间不会导致T细胞无反应性。它们不会释放大量可抑制T细胞反应的可溶性因子。使用RLV感染的DC刺激时T细胞反应较低，可通过添加对照DC来克服。用抗MHC II类分子的单克隆抗体预处理这些对照DC，在存在感染DC的情况下，会完全阻断其恢复T细胞刺激的能力。然而，抗MHC I类或错配的MHC II类分子的抗体并不能阻止功能的恢复。先前报道的表面MHC II类分子标记减少表明细胞内总II类分子的丢失；暴露于病毒后MHC I类水平未改变。与β-肌动蛋白相比，在来自RLV感染小鼠的DC中，MHC II类的生物合成在转录水平上降低了约50%。因此，RLV感染后在DC中观察到的表面II类分子下调是其生物合成中特定阻滞的结果，而DC无法刺激T细胞可能是II类水平降低的直接后果。由于在人类HIV-1感染中也观察到DC刺激减少，我们推测类似的机制可能在人类逆转录病毒感染中起作用。
