Modulation of Th2 responses by peptide analogues in a murine model of allergic asthma: Amelioration or deterioration of the disease process depends on the Th1 or Th2 skewing characteristics of the therapeutic peptide

Allergen-specific CD4(+) Th2 cells play an important role in the immunologi cal processes of allergic asthma, Previously we have shown that, by using t he immunodominant epitope OVA(323-339), peptide immunotherapy in a murine m odel of OVA induced allergic asthma, stimulated OVA-specific Th2 cells, and deteriorated airway hyperresponsiveness and eosinophilia. In the present s tudy, we defined four modulatory peptide analogues of OVA(323-339) with com parable MHC class II binding affinity, These peptide analogues were used fo r immunotherapy by s.c. injection in OVA-sensitized mice before OVA challen ge, Compared with vehicle-treated mice, treatment with the Th2-skewing mild -type peptide and a Th2-skewing partial agonistic peptide (335N-A) dramatic ally increased airway eosinophilia upon OVA challenge, In contrast, treatme nt with a Th1-skewing peptide analogue (336E-A) resulted in a significant d ecrease in airway eosinophilia and OVA-specific IL-4 and IL-5 production, O ur data show for the first time that a Th1-skewing peptide analogue of a do minant allergen epitope can modulate allergen-specific Th2 effector cells i n an allergic response in vivo, Furthermore, these data suggest that the us e of Th1-skewing peptides instead of wild-type peptide may improve peptide immunotherapy and may contribute to the development of a successful and saf e immunotherapy for allergic patients.