INTERLEUKIN-4 PLAYS A DOMINANT ROLE IN TH1- OR TH2-LIKE RESPONSES DURING THE PRIMARY IMMUNE-RESPONSE TO THE HAPTEN PENICILLIN

Despite a large number of studies on the Th1/Th2 balance during immune response to pathogens or protein antigens, little is known concerning the early events which regulate Th1/Th2 differentiation following a s ingle injection of haptenic compounds. In this work, we studied how tw o mouse strains with different MHC haplotypes, SJL (H-2(s)) and Balb/c (H-2(d)), could develop different primary immune responses to subcuta neously injected benzylpenicillin coupled to tetanus toroid (BPO-TT). The SJL mice showed a high BPO-specific IgG1 response that was maximum on day 10 and no BPO-specific IgG2a response. In contrast, Balb/c mic e showed a high BPO-specific IgG2a response on days 15 and 22 and a we ak IgG1 production. In SJL mice, the response to BPO-TT was characteri zed by a very early and high IL-4 mRNA expression. In Balb/c, a delaye d and weaker expression of IL-4 mRNA was observed. Kinetics of IL-2 an d IFN-gamma mRNA expression were comparable in both strains, but IFN-g amma mRNA expression was higher in SJL than in Balb/c. In vivo neutral ization of IL-4 induced a significant BPO-specific IgG2a production an d a two-fold reduction of IgG1 production in SJL mice while it acceler ated production of BPO-specific IgG2a in Balb/c mice. In addition, stu dies of IL-12 p40 and IL-10 mRNA expression following immunization wit h BPO-TT showed a greater IL-12 p40 mRNA expression in Balb/c mice and a slightly higher IL-10 mRNA expression in SJL. Taken together, our d ata suggest that Th1 or Th2 differentiation in primary immune response s to haptenic compounds such as penicillin may be driven by the kineti cs and the level of IL-4 production rather than by the level of IFN-ga mma. Additional cytokines such as IL-10 and IL-12 are likely to contri bute to the regulation of this response.