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Clinical and Diagnostic Laboratory Immunology, January 2000, p. 101-105, Vol. 7, No. 1
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, Buffalo, New York
Received 30 July 1999/Returned for modification 24 September
1999/Accepted 25 October 1999
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-
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Reversal of Human Immunodeficiency Virus Type 1 Protein-Induced Inhibition of Natural Killer Cell Activity by Alpha
Interferon and Interleukin-2
) or
interleukin 2 (IL-2) alone partially reversed the Env-Gag-induced
suppression of NK cell activity. However, LGL treated with both IFN-
and IL-2 completely reversed the suppression of NK cell cytotoxicity by
Env-Gag. The combined effect of IFN-
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.
*
Corresponding author. Mailing address: Research
Professor of Medicine, Buffalo General Hospital, 100 High St., Buffalo,
NY 14203. Phone: (716) 859-2985. Fax: (716) 859-2999. E-mail:
mnair{at}acsu.buffalo.edu.
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