di Marzio P, Mariani R, Lui R, Thomas E K, Landau N R
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Ave, New York, NY 10016, USA.
Cytokine. 2000 Oct;12(10):1489-95. doi: 10.1006/cyto.1999.0594.
CD40 ligand (CD40L) is a cell surface molecule of CD4(+)T cells that interacts with its receptor CD40 on antigen presenting cells to mediate thymus-dependent humoral immunity and inflammatory reactions. We report here that treating monocyte-derived macrophages (MDM) with a trimeric soluble form of CD40L (CD40LT) induced them to secrete high levels of the beta-chemokines RANTES, MIP-1alpha and MIP-1beta that are ligands for CCR5 and able to inhibit HIV-1 entry. CD40LT inhibited the entry of M-tropic HIV-1 reporter viruses. Furthermore, supernatants obtained from CD40LT-stimulated macrophages protected CEMx174-CCR5 cells from infection by HIV-1(JRFL)reporter virus. The inhibitory activity appeared to be due to beta-chemokines present in the supernatant, since pretreating them with a cocktail of antibodies to RANTES, MIP-1alpha and MIP-1beta neutralized the inhibitory activity of the supernatants. In addition, treating monocytes with CD40LT caused CCR5 and CD4 to be downregulated from the cell surface. In vivo, macrophages activated through CD40 could interfere with HIV replication.
CD40配体（CD40L）是CD4(+)T细胞的一种细胞表面分子，它与其在抗原呈递细胞上的受体CD40相互作用，介导胸腺依赖性体液免疫和炎症反应。我们在此报告，用三聚体可溶性形式的CD40L（CD40LT）处理单核细胞衍生的巨噬细胞（MDM）可诱导它们分泌高水平的β趋化因子RANTES、MIP-1α和MIP-1β，这些趋化因子是CCR5的配体，能够抑制HIV-1进入。CD40LT抑制M嗜性HIV-1报告病毒的进入。此外，从CD40LT刺激的巨噬细胞获得的上清液可保护CEMx174-CCR5细胞免受HIV-1（JRFL）报告病毒的感染。这种抑制活性似乎归因于上清液中存在的β趋化因子，因为用针对RANTES、MIP-1α和MIP-1β的抗体混合物预处理它们可中和上清液的抑制活性。此外，用CD40LT处理单核细胞会导致CCR5和CD4从细胞表面下调。在体内，通过CD40激活的巨噬细胞可干扰HIV复制。
