Open AccessRecombinant human IL‐16 inhibits HIV‐1 replication and protects against activation‐induced cell death (AICD)
Author(s) -
Thierry Idziorek,
Jamal Khalife,
Odile Billaut-Mulot,
Emmanuel Hermann,
Marc Aumercier,
Y Mouton,
A Capron,
Bahr Gm
Publication year - 1998
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1998.00550.x
Subject(s) - biology , peripheral blood mononuclear cell , cytokine , recombinant dna , apoptosis , immunology , lymphocyte , immune system , in vitro , biochemistry , gene
The chemoattractant cytokine IL‐16 has been reported to suppress lymphocyte activation and to inhibit HIV‐1 replication in acutely infected T cells. We have cloned and expressed human IL‐16 in Escherichia coli and investigated whether the recombinant protein could regulate the level of lymphocyte apoptosis from HIV‐1‐infected subjects. After purification and refolding, only 2–10% of the recombinant cytokine was present in a biologically active homotetrameric form. This could explain the need for high concentrations of the bacterially derived IL‐16 to induce significant inhibition of HIV‐1 replication. Addition of IL‐16 to unstimulated peripheral blood mononuclear cell (PBMC) cultures from HIV‐1‐infected subjects did not modify the observed level of spontaneous lymphocyte apoptosis. In contrast, IL‐16 added to PBMC cultures stimulated with anti‐CD3, anti‐CD95 or dexamethasone reduced significantly the percentage of lymphocytes undergoing AICD. This effect was found to correlate with the ability of the cytokine to decrease CD95 expression on activated CD4 + T cells. Comparative studies on PBMC from healthy individuals indicated that the regulation of apoptosis levels by IL‐16 is a complex phenomenon and could depend on the nature of the activator used and/or the immune status of lymphocytes tested. The outcome of CD4 cross‐linking on T cells by various ligands is discussed in the context of the observed beneficial activities of IL‐16 and its potential role in the treatment of HIV disease.