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Production In Vitro1
*
Department of Immunology and Medical Zoology, Faculty of Medicine, Fukui Medical University, Yoshida-gun, Fukui, Japan;
Department of Bacterial and Blood Products, National Institute of Infectious Diseases, Musashimurayamashi, Tokyo, Japan; and
Department of Hematology and Clinical Immunology, Kobe City General Hospital, Kobe, Japan.
Previous studies have shown that the action of bacterial or
synthetic oligodeoxynucleotide (oligo-DNA) on mouse NK cells to produce
IFN-
is mediated mostly by monocytes/macrophages activated by
olig-DNA. However, its action on human IFN--producing cells has not
been well investigated. In the present study, we examined the effect of
oligo-DNAs on highly purified human NK and T cells. Bacillus
Calmette-Guérin-derived or synthetic oligo-DNAs induced NK cells
to produce IFN- with an increased CD69 expression, and the autocrine
IFN- enhanced their cytotoxicity. The response of NK cells to
oligo-DNAs was enhanced when the cells were activated with IL-2, IL-12,
or anti-CD16 Ab. T cells did not produce IFN- in response to
oligo-DNAs but did respond independently of IL-2 when they were
stimulated with anti-CD3 Ab. In the action of oligo-DNAs, the
palindrome sequence containing unmethylated 5'-CpG-3' motif(s) appeared
to play an important role in the IFN--producing ability of NK cells.
The changes of base composition inside or outside the palindrome
sequence altered its activity: The homooligo-G-flanked GACGATCGTC
was the most potent IFN- inducer for NK cells. The CG palindrome was
also important for activated NK and T cells in their IFN-
production, although certain nonpalindromes acted on them. Among the
sequences tested, cell activation- or cell lineage-specific sequences
were likely; i.e., palindrome ACCGGT and nonpalindrome AACGAT were
favored by activated NK cells but not by unactivated NK cells or
activated T cells. These results indicate that oligo-DNAs containing CG
palindrome act directly on human NK cells and activated T cells to
induce IFN- production.
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