Oligodeoxynucleotides containing palindrome sequences with internal 5'-CpG-3' act directly on human NK and activated T cells to induce IFN-gamma production in vitro.
Previous studies have shown that the action of bacterial or synthetic oligodeoxynucleotide (oligo-DNA) on mouse NK cells to produce IFN-gamma is mediated mostly by monocytes/macrophages activated by olig-DNA. However, its action on human IFN-gamma-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-gamma with an increased CD69 expression, and the autocrine IFN-gamma 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-gamma 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-gamma-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-gamma inducer for NK cells. The CG palindrome was also important for activated NK and T cells in their IFN-gamma 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-gamma production.
Iho
S
S
Department of Immunology, Faculty of Medicine, Fukui Medical University, Japan. ihosumik@fmsrsa.fukui-med.ac.jp
Yamamoto
T
T
Takahashi
T
T
Yamamoto
S
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D002469:Cell Separation; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000235:genetics; D004269:DNA, Bacterial / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000502:physiology; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009163:Mycobacterium bovis / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000494:pharmacology*; D017452:Receptors, IgG / Q000276:immunology; D012091:Repetitive Sequences, Nucleic Acid / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D000099192:CD69 Antigens
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D004269:DNA, Bacterial; D007371:Interferon-gamma; D018664:Interleukin-12; D007376:Interleukin-2; D037181:Lectins, C-Type; D009838:Oligodeoxyribonucleotides; D017452:Receptors, IgG; D000099192:CD69 Antigens