Abstract
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 β-chemokines RANTES, MIP-1α and MIP-1β 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-1JRFLreporter virus. The inhibitory activity appeared to be due to β-chemokines present in the supernatant, since pretreating them with a cocktail of antibodies to RANTES, MIP-1α and MIP-1β 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.
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