Masurier C, Salomon B, Guettari N, Pioche C, Lachapelle F, Guigon M, Klatzmann D
Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Université Pierre et Marie Curie/CNRS ESA 70-87, Hôpital Pitié-Salpêtrière, Paris, France.
J Virol. 1998 Oct;72(10):7822-9. doi: 10.1128/JVI.72.10.7822-7829.1998.
We have developed a murine model to study the involvement of dendritic cells (DC) in human immunodeficiency virus (HIV) routing from an inoculation site to the lymph nodes (LN). Murine bone marrow-derived DC migrate to the draining LN within 24 h after subcutaneous injection. After incubation of these cells with heat-inactivated (Hi) HIV type 1 (HIV-1), HIV RNA sequences were detected in the draining LN only. Upon injection of DC pulsed with infectious HIV, the virus recovered in the draining LN was still able to productively infect human T cells. After a vaginal challenge with Hi HIV-1, the virus could be detected in the iliac and sacral draining LN at 24 h after injection. After an intravenous challenge, the virus could be detected in peripheral LN as soon as 30 min after injection. The specific depletion of a myeloid-related LN DC population, previously shown to take up blood macromolecules and to translocate them into the LN, prevented HIV transport to LN. Together, our data demonstrate the critical role of DC for HIV routing to LN after either a vaginal or an intravenous challenge, which does not require their infection. Therefore, despite the fact that the mouse is not infectable by HIV, this small animal model might be useful to test preventive strategies against HIV.
我们开发了一种小鼠模型，用于研究树突状细胞（DC）在人类免疫缺陷病毒（HIV）从接种部位转移至淋巴结（LN）过程中的作用。小鼠骨髓来源的DC在皮下注射后24小时内迁移至引流淋巴结。将这些细胞与热灭活（Hi）的1型人类免疫缺陷病毒（HIV-1）孵育后，仅在引流淋巴结中检测到HIV RNA序列。注射用感染性HIV脉冲处理的DC后，在引流淋巴结中回收的病毒仍能够有效感染人类T细胞。用Hi HIV-1进行阴道攻击后，在注射后24小时可在髂骨和骶骨引流淋巴结中检测到病毒。静脉注射攻击后，在注射后30分钟即可在外周淋巴结中检测到病毒。先前显示可摄取血液大分子并将其转运至淋巴结的髓样相关淋巴结DC群体的特异性耗竭，可阻止HIV转运至淋巴结。总之，我们的数据证明了DC在阴道或静脉注射攻击后对HIV转运至淋巴结的关键作用，这并不需要DC被感染。因此，尽管小鼠不能被HIV感染，但这种小动物模型可能有助于测试针对HIV的预防策略。
