Recombinant human IL-16 inhibits HIV-1 replication and protects against activation-induced cell death (AICD).
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.
Idziorek
T
T
Institut Pasteur de Lille, INSERM U167, France.
Khalife
J
J
Billaut-Mulot
O
O
Hermann
E
E
Aumercier
M
M
Mouton
Y
Y
Capron
A
A
Bahr
G M
GM
D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004926:Escherichia coli; D015658:HIV Infections / Q000097:blood* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D019410:Interleukin-16 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000821:virology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014779:Virus Replication / Q000276:immunology*
D019410:Interleukin-16; D011994:Recombinant Proteins