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

• Published in: Clinical and experimental immunology Vol. 132; no. 2; pp. 289 - 296
• Main Authors: BAHR, G. M., DARCISSAC, E. C. A., MOUTON, Y.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.05.2003; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: antigen‐presenting cells; Biological and medical sciences; CD4 Antigens - genetics; Cells, Cultured; chemokines; Clinical Studies; Culture Media, Conditioned; Cytokines - metabolism; Dendritic Cells - immunology; Dendritic Cells - virology; Flow Cytometry; Gene Expression - drug effects; HIV Infections - immunology; HIV-1; Human viral diseases; Humans; IL‐2; Infectious diseases; Interleukin-2 - pharmacology; Macrophages - immunology; Macrophages - virology; Medical sciences; Receptors, CCR5 - genetics; Receptors, CXCR4 - genetics; Reverse Transcriptase Polymerase Chain Reaction; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; virus receptors; Virus Replication - drug effects; Immunopathology; Dendritic cell; Immune response; HIV-1 virus; Cytokine; Retroviridae; AIDS; Chemokine receptor; Immune deficiency; Lentivirus; Infection; Virus; Interleukin 2; antigen-presenting cells chemokines HIV-1 IL-2 virus receptors; Antigen presenting cell; Viral disease; Replication; Human immunodeficiency virus; Infected cell; CXCR4 chemokine receptor; Biological receptor; Macrophage
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.2003.02143.x

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.