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

Abstract: CD40 ligand (CD40L), expressed on activated T cells, binds its receptor, CD40, on dendritic cells, B cells, and monocytes/macrophages. Human immunodeficiency virus (HIV)‐infected individuals exhibit normal B‐cell CD40 expression but diminished expression of CD40L on CD4 + T cells. Thus, we studied recombinant human CD40L (huCD40L) in an in vitro rhesus macaque model of acquired immunodeficiency syndrome (AIDS). huCD40L induced peripheral blood mononuclear 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 chain reaction (RT‐PCR) analysis showed reduced expression of SIV gag and increased expression of interleukin (IL)‐16 mRNA. Supernatants from huCD40L‐stimulated PBMC and control cultures contained similar amounts of IL‐16, suggesting an intracellular antiviral effect by IL‐16. Phytohemagglutinin (PHA)‐stimulated PBMCs similarly cultured with huCD40L showed only slight increases in chemokine production (P > 0.05). These results suggest that huCD40L inhibits replication (antigen and mRNA production) of SIVmac239. This response involves huCD40L induction of IL‐16 mRNA expression and appears to be independent of β‐chemokines.