Ayehunie S, Groves R W, Bruzzese A M, Ruprecht R M, Kupper T S, Langhoff E
Laboratory of Viral Pathogenesis, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
AIDS Res Hum Retroviruses. 1995 Aug;11(8):877-84. doi: 10.1089/aid.1995.11.877.
Most human immunodeficiency virus type 1 (HIV-1) infections involve sexual contact and virus passage across mucosal surfaces. While Langerhans cells (LCs) and dendritic cells (DCs) have been implicated in mucosal infection, their role is undefined. Here we demonstrate that acutely HIV-1-infected LCs and DCs effectively transmit virus to uninfected, activated T cells. Cocultivation of these cells results in massive virus production that requires a short cell-cell contact; as little as 30 min contact time is sufficient for HIV-1-pulsed DCs to infect their target T cells. Furthermore, surface-bound virus inactivation by trypsin does not significantly decrease the efficiency of virus transmission by LC/DCs, suggesting rapid internalization of virus. This effective virus transfer by infected LCs and blood-derived DCs requires prior activation of T cells. Surprisingly, cocultivation of acutely infected T cells with uninfected, activated target T cells results only in low virus production, even with T cell-tropic virus. We conclude that LCs and DCs are not only important targets of HIV-1 infection, but may also play a key role in the early dissemination of virus to T cells they encounter in skin or lymphoid tissue.
大多数1型人类免疫缺陷病毒(HIV-1)感染涉及性接触以及病毒穿过黏膜表面。虽然朗格汉斯细胞(LCs)和树突状细胞(DCs)与黏膜感染有关,但其作用尚不明确。在此我们证明,急性HIV-1感染的LCs和DCs能有效地将病毒传递给未感染的活化T细胞。这些细胞的共培养导致大量病毒产生,这需要短时间的细胞-细胞接触;HIV-1脉冲DCs与靶T细胞接触仅30分钟就足以感染靶T细胞。此外,胰蛋白酶对表面结合病毒的灭活并不会显著降低LCs/DCs传递病毒的效率,这表明病毒能迅速内化。被感染的LCs和血液来源的DCs进行的这种有效病毒传递需要T细胞预先活化。令人惊讶的是,急性感染的T细胞与未感染的活化靶T细胞共培养仅产生少量病毒,即使是嗜T细胞病毒也是如此。我们得出结论,LCs和DCs不仅是HIV-1感染重要靶细胞且在病毒早期传播至它们在皮肤或淋巴组织中遇到的T细胞过程中可能起关键作用。