Recombinant human CD40 ligand inhibits simian immunodeficiency virus replication: A role for interleukin-16

CD40 ligand (CD40L), expressed on activated T cells, binds its receptor, CD 40, on dendritic cells, B cells, and monocytes/macrophages. Human immunodef iciency virus (HIV)-infected individuals exhibit normal B-cell CD40 express ion but diminished expression of CD40L on CD4(+) T cells. Thus. we studied recombinant human CD40L (huCD40L) in an in vitro rhesus macaque model of ac quired immunodeficiency syndrome (AIDS). huCD40L induced peripheral blood m ononuclear cell (PBMC) proliferation independent of mitogenic cytokines and led to a 70% reduction in p27 production by simian immunodeficiency virus (SIV) mac239 infected PBMCs (P < 0.05). Reverse transcriptase-polymerase ch ain reaction (RT-PCR) analysis showed reduced expression of SIV gag and inc reased expression of interleukin (IL)-16 mRNA. Supernatants from huCD40L-st imulated PBMC and control cultures contained similar amounts of IL-16, sugg esting an intracellular antiviral effect by IL-16. Phytohemagglutinin (PHA) -stimulated PBMCs similarly cultured with huCD40L showed only slight increa ses in chemokine production (P > 0.05). These results suggest that huCD40L inhibits replication (antigen and mRNA production) of SIVmac239. This respo nse involves huCD40L induction of IL-16 mRNA expression and appears to be i ndependent of beta-chemokines.