REGULATION OF HOUSE-DUST MITE RESPONSES BY INTRANASALLY ADMINISTERED PEPTIDE - TRANSIENT ACTIVATION OF CD4(-CELLS PRECEDES THE DEVELOPMENT OF TOLERANCE IN-VIVO() T)

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 antigen-specific CD4(+) T cell re sponses in H-2(b) mice. Here we report that i.n. peptide induced a rap id but transient activation of MHC class II restricted CD4(+) T cells that peaked 4 days after peptide treatment and was of similar magnitud e 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 1 11-139; however, by day 14 IL-2 and IFN-gamma secretion by T cells wer e down-regulated. Mice deficient in CD8(+) T cells became tolerant by i.n. treatment with peptide, suggesting that CD8(+) T cells are not in volved in down-regulating the CD4(+) T cell response. Rechallenging mi ce with a single dose of p1 111-139 21 days after the initial treatmen t 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 i.n. e xposures to p1 111-139. Our findings address the mechanisms underlying peripheral T cell tolerance following i.n. administration of a high d ose of immunogenic peptide and have implications for understanding the consequences of peptide immunotherapy.