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 found 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 CD4 molecules, to be susceptible to HIV-1 infection and to play a critical role in different immune processes. Therefore, we evaluated the ability of recombinant IL-16 (rIL-16) to regulate receptor expression and cytokine release in monocyte-derived macrophages (MDM) and monocyte-derived dendritic cells (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 CD83 was consistently detected. Furthermore, the level of gene expression of the chemokine receptors CCR5 and CXCR4 was significantly reduced in rIL-16-treated MDM and costimulation with IL-2 did not modify the activity of the recombinant cytokine. The effects on chemokine receptor gene expression were less evident in MDDC and only a transient down-regulation of weak intensity could be detected following stimulation with rIL-16. Analysis of supernatants from rIL-16-stimulatedcultures revealed a different profile of released cytokines/chemokines among the two cell populations studied. These findings 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-1 infection.
Hermann
E
E
Institut Pasteur de Lille, INSERM U167, Lille, France.
Darcissac
E
E
Idziorek
T
T
Capron
A
A
Bahr
G M
GM
D015703:Antigens, CD / Q000378:metabolism*; D015704:CD4 Antigens / Q000235:genetics; D018929:Cell Culture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D006801:Humans; D016130:Immunophenotyping; D019410:Interleukin-16 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015703:Antigens, CD; D015704:CD4 Antigens; D016207:Cytokines; D019410:Interleukin-16; D012333:RNA, Messenger; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011994:Recombinant Proteins