Recombinant interleukin-16 selectively modulates surface receptor expression and cytokine release in macrophages and dendritic cells

Interleukin-16 (IL-16), a natural ligand for the CD4 receptor, has been fou nd to modulate T-lymphocyte function and to inhibit human immunodeficiency virus type 1 (HIV-1) replication. Antigen-presenting cells (APC), including macrophages and dendritic cells, are known to express functional surface C D4 molecules, to be susceptible to HIV-I infection and to play a critical r ole in different immune processes. Therefore, we evaluated the ability of r ecombinant IL-16 (rIL-16) to regulate receptor expression and cytokine rele ase in monocyte-derived macrophages (MDM) and monocyte-derived dendritic ce lls (MDDC). Recombinant IL-16 was found to up-regulate CD25 and CD80 but to down-regulate CD4 and CD86 surface expression in MDM cultures. However, no change could be observed on the level of CD4, CD80 and CD86 expression in IL-16-stimulated MDDC, although a significant up-regulation of CD25 and CD8 3 was consistently detected. Furthermore, the level of gene expression of t he chemokine receptors CCR5 and CXCR4 was significantly reduced in rIL-16-t reated MDM and costimulation with IL-2 did not modify the activity of the r ecombinant cytokine. The effects on chemokine receptor gene expression were less evident in MDDC and only a transient down-regulation of weak intensit y could be detected following stimulation with rIL-16. Analysis of supernat ants from rIL-16-stimulated-cultures revealed a different profile of releas ed cytokines/chemokines among the two cell populations studied. These findi ngs establish an important role for IL-16 in modulating the activity of APC and may have relevance regarding the protection of reservoir cells against HIV-I infection.