Effect of cytokine-specific antisense oligonucleotides on the immunoglobulin production by rat spleen cells in vitro.
We examined in this study the regulation of immunoglobulin (IgM, IgG, IgE) production by spleen cells from N brasiliensis infected rats following addition of antisense oligodeoxynucleotides (ODNs). The ODNs were selected near the AUG initiation codon of mRNA specific for interleukin 4 (IL-4) or interleukin 2 (IL-2). Results show that addition of antisense to IL-4 inhibited IgE production, while the production of IgG and IgM increased. The use of sense IL-4 sequence did not affect immunoglobulin production. In contrast, the use of antisense IL-2 ODN induced an enhancement of IgE as well as of IgM and IgG responses. Both the Ig secretion in culture supernatants and the number of Ig secreting cells, as detected by an Elispot assay, were influenced by the presence of antisense IL-4 ODNs. These results clearly show the involvement of IL-2 and IL-4 in the regulation of isotype selection during antibody synthesis and that IL-2 and IL-4 do operate differently on IgE production. They also argue that antisense strategy represents a useful tool for the antibody regulation.
Laboratoire de biologie des cytokines, CHRU, Reims, France.
N
N
Benbernou
P
P
Matsiota-Bernard
M
M
Guenounou
D000818:Animals; D001483:Base Sequence; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D007136:Immunoglobulins / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D007136:Immunoglobulins; D007376:Interleukin-2; D016376:Oligonucleotides, Antisense; D015847:Interleukin-4