Reversal of human immunodeficiency virus type 1 protein-induced inhibition of natural killer cell activity by alpha interferon and interleukin-2.
A recombinant fusion peptide, Env-Gag, derived from the human immunodeficiency virus type 1 (HIV-1) genome corresponding to a defined portion of the envelope (Env) and internal core (Gag) proteins was examined for immunoregulatory effects on the cytotoxic activity of natural killer (NK) cell-enriched, large granular lymphocytes (LGL) from healthy donors. Percoll-separated, NK cell-enriched LGL precultured for 24 h with Env-Gag at 10- and 50-ng/ml concentrations, which significantly stimulated lymphocyte proliferation, caused significant suppression of NK cell activity. Denatured Env-Gag did not cause any effect on the NK cell activity of LGL. Two other control peptides, one derived from the Escherichia coli vector used to clone the HIV Env-Gag fusion peptide and the other derived from a non-HIV-1 viral antigen (rubeola virus), did not produce any observable effect on the NK cell activity of LGL, demonstrating the specificity of the effect produced by Env-Gag. Subsequent treatment of LGL with alpha interferon (IFN-alpha) or interleukin 2 (IL-2) alone partially reversed the Env-Gag-induced suppression of NK cell activity. However, LGL treated with both IFN-alpha and IL-2 completely reversed the suppression of NK cell cytotoxicity by Env-Gag. The combined effect of IFN-alpha and IL-2 in enhancing NK cell activity may provide a novel therapeutic approach to the restoration of depressed NK cell activity observed in HIV-infected patients.
Nair
M P
MP
Department of Medicine and Microbiology, Division of Allergy, Immunology and Rheumatology, and Buffalo General Hospital, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, New York 14203, USA. mnair@acsu.buffalo.edu
Schwartz
S A
SA
D004926:Escherichia coli / Q000235:genetics; D016655:HIV Core Protein p24 / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects*; D008213:Lymphocyte Activation; D008457:Measles / Q000378:metabolism; D011994:Recombinant Proteins
D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins