Oral administration of a dominant T-cell determinant peptide inhibits allergen-specific TH1 and TH2 cell responses in Cry j 2–primed mice

Background: Oral immunotherapy with a peptide for allergic immune responses is theoretically a promising therapy but has not been established yet. Objective: To evaluate immune suppressive efficacy of oral administration of an immunodominant peptide, we investigated changes in T-cell proliferation, T_H1 - and T_H2 -cytokine production, and T_H1 - and T_H2 -mediated antibody production in mice after oral administration of a peptide. Methods: Peptide p246-259, containing a dominant T-cell determinant of Cry j 2, which is the major allergen in Japanese cedar pollen, was used in this study. Groups of mice received p246-259 or PBS alone before or after they were primed intranasally with Cry j 2 and cholera toxin. In another experiment mice were primed intraperitoneally with Cry j 2 and alum. Proliferative response and cytokine production by nasal-associated lymph node cells against Cry j 2 were investigated. Amounts of systemic anti-Cry j 2 IgE and IgG antibodies were also measured. Results: Oral administration of the peptide to mice before, or even after, the sensitization induced oral tolerance in T-cell responses against the allergen; the tolerance was associated with decreased production of T_H1 (IFN-γ and IL-2) and T_H2 (IL-4) cytokines. Allergen-specific T_H1 -mediated (IgG2a and IgG2b) and T_H2 -mediated (IgG1 and IgE) antibody responses were also inhibited. Conclusions: Oral administration of a dominant T-cell determinant peptide induces immunologic tolerance in both T_H1 and T_H2 cell responses against the whole protein allergen. Our study is the first, to our knowledge, to demonstrate the potential for peptide-based oral immunotherapy in order to treat allergic immune responses. (J Allergy Clin Immunol 1998;102:961-7.)