Suppression of asthma-like responses in different mouse strains by oral tolerance

In this study we examined the effect of oral antigen (Ag) administration on the development of experimental asthma in different mouse strains. We sele cted BALB/c, BP2, CBA/Ca interleukin (IL)-5 transgenic, and BALB/c T-cell r eceptor-delta -deficient mouse strains because they exhibit different aspec ts of the asthma syndrome. Mice exposed to 1% ovalbumin (OVA), dissolved in the drinking water for 5 consecutive days, became unresponsive to subseque nt immunogenic OVA challenges. This regimen of OVA administration induced A g-specific unresponsiveness in all mouse strains tested, including gamma de lta -deficient mice that are said to be resistant to tolerance induction. T he Ag-specific unresponsiveness was characterized by reduced (almost absent ) airway eosinophilic inflammation, airway hyperreactivity, and mucus produ ction; also by low levels of T helper (Th) 2-type cytokines in bronchoalveo lar ravage fluid, and decreased immunoglobulin (ig) G1 and IgE OVA-specific antibody production. The unresponsive state was not associated with increa sed levels of the suppressive cytokines IL-10 and transforming growth facto r (TGF)-beta or with immune deviation toward the Th1 pathway due to increas ed levels of interferon-gamma and IL-12. Moreover, treatment with anti-TGF- beta antibodies did not abrogate oral tolerance. Oral Ag administration was quite effective in suppressing the development of key features of asthma w hen initiated after primary immunization (Day 0) or after booster (Day 7), but not after challenge (Day 14) when it increased allergic responses. Coll ectively, our findings show for the first time the beneficial and detriment al effects of oral Ag administration on the development of experimental ast hma.