IMMUNOLOGICAL RESPONSES FOLLOWING RESPIRATORY SENSITIZATION TO HOUSE-DUST MITE ALLERGENS IN MICE

Allergens from the house dust mite Dermatophagoides pteronyssinus are a major cause of human respiratory diseases, including asthma. In orde r to help in understanding the early events in allergen sensitization, a murine model of allergic respiratory disease was developed. Mice we re immunized by intranasal inoculation of Der p 1 or Der p 2 on days 0 , 3, 7, 10, 13, 17, 21 and 29. T cell reactivity was determined using in vitro assays of allergen-specific cytokine production by cells from the spleen, the draining superficial cervical lymph nodes (SCLN) and the non-draining brachial and inguinal nodes, The cytokines assayed in supernatants were IL-4. as a measure of Th2 activation, IL-2 as a mea sure of Th 1 activation, and IL-3/GM-CSF as an overall marker of T cel l stimulation. There was evidence of local and systemic T cell activat ion by day 7, with the release of IL-2 and of IL-3/GM-CSF by SCLN and spleen cells, respectively. IL-4 production by SCLN and spleen cells w as not evident until day 21. T cell sensitization in non-draining node groups was not detected. Intradermal skin tests were performed at the above specified times and positive wheal responses indicated that spe cific IgE was present from day 3. The above data suggest that respirat ory immunization to allergen is rapid and is associated with early sys temic sensitization. In this model both Th1 and Th2 responses were evi dent. with the Th I response occurring early and the Th2 following aft er repeated immunizations.