Induction of Th-1 and Th-2 responses by respiratory syncytial virus attachment glycoprotein is epitope and major histocompatibility complex independent

In BALB/c mice, sensitization to respiratory syncytial virus (RSV) attachme nt (G) glycoprotein leads to the development of lung eosinophilia upon chal lenge infection with RSV, a pathology indicative of a strong in vivo induct ion of a Th-2-type response. In this study, we found that a strong, RSV G-s pecific, Th-1-type cytokine response occurred simultaneously with a Th-2-ty pe response in G-primed mice after RSV challenge. Both Th-l and Th-2 effect or CD4(+) T cells recognized a single immunodominant site on this protein, implying that the differentiation of memory CD4(+) T cells along the Th-1 o r Th-2 effector pathway was independent of the epitope specificity of the T cells. A similar observation was made in G-primed H-2(b) haplotype mice af ter RSV challenge, further suggesting that this process is not dependent on the peptide epitope presented. On the other hand, genes mapping to loci ou tside of the major histocompatibility complex region are crucial regulators of the development of a Th-2-type response and lung eosinophilia. The impl ication of these findings for the immune mechanisms underlying the pathogen esis of RSV is discussed.