A high-molecular-weight mite antigen (HM1) fraction aggravates airway hyperresponsiveness of allergic mice to house dusts and whole mite cultures.

BACKGROUND: The house dust mite Dermatophagoides farinae is the most common aeroallergen causing human allergic asthma. Previously, we demonstrated that a high-molecular-weight allergenic fraction (HM1), which was abundant in D. farinae extracts, induced a proliferative response of T cells from healthy donors. The induction was mediated through the activation of macrophages without MHC class II restriction. In this study, we investigate whether HM1 influences the development of airway inflammation in murine models of asthma. METHODS: BALB/c mice were injected twice intraperitoneally with D. farinae fecal extract (Dff) at an interval of 5 days. They were exposed daily to aerosolized antigen (group 1: Dff, group 2: HM1, group 3: HM1-depleted Dff and group 4: PBS) for 10 days. The effect of HM1 on their airway inflammation was evaluated by measuring acetylcholine-induced airway hyperresponsiveness and inflammatory cell infiltration in lung tissue. RESULTS: The inhalation of the whole fecal extract or the HM1 fraction induced airway hyperresponsiveness which was detectable after 24 h and was maintained for as long as 120 h. The inhalation of extract depleted of the HM1 fraction induced hyperresponsiveness measured at 24 h but this was not maintained for 120 h. Macrophage infiltration was significantly prolonged in mice inhaling the whole extract and the HM1 fraction compared to the HM1-depleted extract. CONCLUSION: The inhalation of the high-molecular-weight HM1 fraction of D. farinae prolonged airway hyperresponsiveness and macrophage inflammation in a mouse model of hypersensitivity. The results indicate that the HM1 fraction which can induce T cell proliferation through macrophage activation may play a role in the duration of airway responsiveness.

Induction of a proliferative response of T cells by a high-molecular antigen in Dermatophagoides farinae feces.

BACKGROUND: We have previously demonstrated that high-molecular mite antigen (HM1) from Dermatophagoides farinae feces is an allergen which binds to mite-allergic patients IgE. HM1 also induced a proliferative response in lymph node cells from mite-immunized mice as well as nonimmunized mice. In the present study, we demonstrated that HM1 induced T cell proliferation and investigated the HM1-stimulated T cell proliferative pathways using nonallergic human peripheral blood mononuclear cells (PMBC). METHODS: Blood samples were obtained from 10 healthy donors. Using primary culture, T cell response stimulated with HM1 was performed on purified T cells, CD19+ cell-depleted PBMC and CD11b+ cell-depleted PBMC. In addition, interleukin (IL)-5 and interferon (IFN)-gamma produced by mite-allergic and healthy donors stimulated with HM1 were estimated by enzyme immunoassay. RESULTS: T cell proliferation was detected only in CD19+ cell-depleted PBMC. When T cells were cocultured with CD11b+ cells they recovered their proliferative response to HM1. In addition, the pathway of HM1-stimulated T cell proliferation did not involve HLA class II restriction. Both activated CD11b+ cells and their conditioned media were needed to induce HM1-stimulated T cell proliferation. Furthermore, HM1 induced IFN-gamma production in both healthy and allergic donors. CONCLUSION: The high-molecular mite antigen, HM1, induced a proliferative response of T cells in healthy as well as allergic donors, without HLA class II restriction. Our results suggest that further investigation of HM1 could constitute a valuable avenue of research into complex allergic diseases.