Effect of different chemically modified oligodeoxynucleotides on immune stimulation.
Based on previous studies that certain oligonucleotides can stimulate cell proliferation and immunoglobulin production, this study was carried out to establish the relationship between the stimulatory effect and the chemical modification of the oligonucleotide. First, the effects of oligonucleotide and analogs on immune stimulation were studied in vitro using murine splenic lymphocytes. Our results show that cell proliferation and immunoglobulin production (IgG and IgM) depend on the sequence and the chemical modification of the oligonucleotide. Phosphorothioate oligodeoxynucleotides displayed a greater stimulatory effect than partially modified phosphorothioate oligonucleotides. Second, we studied the effects of these chemically modified oligonucleotides after injection in mice. Massive splenomegaly and stimulation of cell proliferation were observed with some phosphorothioate oligonucleotides. These effects were minimized markedly by chimeric and hybrid oligonucleotides. We also demonstrate that in vitro the effects of oligonucleotides on murine lymphocytes were unaffected by T cell depletion, suggesting that oligonucleotides exert their effects mainly on the B cells.
Zhao
Q
Q
Hybridon, Inc., Worcester, MA 01605, USA.
Temsamani
J
J
Iadarola
P L
PL
Jiang
Z
Z
Agrawal
S
S
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D007136:Immunoglobulins / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008934:Mitogens; D008969:Molecular Sequence Data; D020319:Oligodeoxyribonucleotides, Antisense; D009841:Oligonucleotides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000187:drug effects; D013873:Thionucleotides / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D007136:Immunoglobulins; D008934:Mitogens; D020319:Oligodeoxyribonucleotides, Antisense; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; C079996:GEM91