THE SECONDARY ANTIGEN-SPECIFIC IGE RESPONSE IN MURINE LYMPHOCYTES IS RESISTANT TO BLOCKADE BY ANTI-IL4 ANTIBODY AND AN ANTISENSE OLIGODEOXYNUCLEOTIDE FOR IL4 MESSENGER-RNA

In order to investigate the role of interleukin 4 (IL-4) in the induction of antigen-specific IgE responses, we established culture of conditions which allow the induction of anti-trinitrophenyl(TNP) IgE response by the coculture of TNO-keyhole limpet hemocyanin-primed C3H B cells with conalbumin (CA)-specific type 2 helper T (Th2) cel clone, D10.G4.1 in the presence of TNP-CA. A maximum level of anti-TNP IgE was secreted at 1 μg/ml TNP-CA. By using filter-separted double-chamber culture plates, the physical contact between T cells and B cells was shown to be necessary in this respnse. Anti-TNP IgE synthesis was not significantly suppressed in the presence of 20-40 μg/ml monoclonal anti-IL4 (11B11), nor was the response further enhanced by the addition of recombinant IL4. 11B11 added together with anti-IL5 had also no suppressive effects on the IgE response. This apparent independence on Il4 might be due to the fact that IL4 is transferred from T cells in a transsynaptical way that wold be refractory to the neutralization by 11B11. In order to test this possibility, we synthesized the phosphorothioate analogue of an antisense oligodeoxynucleotide against Il4 mRNA (S-oligo) for inhibiting IL4 production from Th2 cells specifically. S-oligo was effective at 10-20 μg/ml in suppressing IL4 production from D10.G4. © 1993 Academic Press, Inc.