Discordant effects of interleukin-2 on viral and immune parameters in human immunodeficiency virus-1-infected monocyte-derived mature dendritic cells

Abstract

SUMMARY Use of interleukin-2 (IL-2) in the immunotherapy of human immunodeficiency virus (HIV) has frequently resulted in the restoration of CD4 lymphocyte counts but not of virus-specific responses. We reasoned that the absence of reconstituted functional immune parameters could be related to the inability of IL-2 to correct HIV-induced dysfunctions in antigen-presenting cells. In this study, we used in vitro-differentiated monocyte-derived macrophages (MDMs) and mature dendritic cells (MDDCs), acutely infected with primary HIV-1 isolates, to analyse the effects of IL-2 on virus replication, co-receptor expression, and cytokine or chemokine release. Stimulation of MDMs with IL-2 had no measurable effect on HIV-1 replication, on cytokine secretion, or on CD4 and CXCR4 gene expression. Moreover, although a significant down-regulation of CCR5 mRNA expression could be repeatedly detected in MDMs, this IL-2-mediated effect was not of substantial magnitude to affect virus replication. On the other hand, IL-2 stimulation of MDDCs dramatically increased HIV-1 replication and this effect was highly evident on low-replicating, CXCR4-dependent isolates. Nevertheless, the HIV-enhancing activity of IL-2 in MDDCs was not accompanied by any measurable change in cytokine or chemokine release, in virus receptor and co-receptor mRNA accumulation, or in the surface expression of a battery of receptors implicated in virus entry, cell activation or costimulatory function. Taken together, these findings point to a role for IL-2 in inducing virus purging from dendritic cell reservoirs but indicate no relevant potential of the cytokine in restoring defective elements of innate immunity in HIV infection.