Regulation of house dust mite responses by intranasally administered peptide: transient activation of CD4+ T cells precedes the development of tolerance in vivo

Abstract

We have previously demonstrated that intranasal (i.n.) administration of an immunodominant peptide (p1 111–139) derived from the house dust mite (HDM) allergen Der p 1 inhibits antigenspecific CD4⁺ T cell responses in H-2^b mice. Here we report that i.n. peptide induced a rapid but transient activation of MHC class II restricted CD4⁺ T cells that peaked 4 days after peptide treatment and was of similar magnitude to that induced by parenteral immunization with antigen in adjuvant. During the early phase of the response lymph node and splenic T cells secreted a range of lymphokines when re-stimulated in vitro with p1 111–139; however, by day 14 IL-2 and IFN-^γ secretion by T cells were down-regulated. Mice deficient in CD8⁺ T cells became tolerant by i.n. treatment with peptide, suggesting that CD8⁺ T cells are not involved in down-regulating the CD4⁺ T cell response. Rechailenging mice with a single dose of p1 111–139 21 days after the initial treatment elicited a further transient T cell response, which was subsequently down-regulated over time. Although the i.n. peptide induced a strong transient CD4⁺ T cell response, only low levels of peptide-specific antibodies were detected either after the initial or subsequent in. exposures to p1 111–139. Our findings address the mechanisms underlying peripheral T cell tolerance following i.n. administration of a high dose of Immunogenic peptide and have implications for understanding the consequences of peptide immunotherapy.