Am. J. Respir. Cell Mol. Biol., Volume 24, Number 5, May, 2001 518-526

Suppression of Asthma-like Responses in Different Mouse Strains by Oral Tolerance

Momtchilo Russo, Marie-Anne Nahori, Jean Lefort, Eliane Gomes, Alexandre de Castro Keller, Dunia Rodriguez, Orlando Garcia Ribeiro, Sahil Adriouch, Vallerie Gallois, Ana M. C. de Faria, and B. Boris Vargaftig

Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil; Institut Pasteur Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-INSERM U485; and Laboratoire d'Immuno-differenciation, Université Paris, Paris, France

In this study we examined the effect of oral antigen (Ag) administration on the development of experimental asthma in different mouse strains. We selected BALB/c, BP2, CBA/Ca interleukin (IL)-5 transgenic, and BALB/c T-cell receptor--deficient mouse strains because they exhibit different aspects of the asthma syndrome. Mice exposed to 1% ovalbumin (OVA), dissolved in the drinking water for 5 consecutive days, became unresponsive to subsequent immunogenic OVA challenges. This regimen of OVA administration induced Ag-specific unresponsiveness in all mouse strains tested, including -deficient mice that are said to be resistant to tolerance induction. The Ag-specific unresponsiveness was characterized by reduced (almost absent) airway eosinophilic inflammation, airway hyperreactivity, and mucus production; also by low levels of T helper (Th) 2-type cytokines in bronchoalveolar lavage fluid, and decreased immunoglobulin (Ig) G1 and IgE OVA-specific antibody production. The unresponsive state was not associated with increased levels of the suppressive cytokines IL-10 and transforming growth factor (TGF)- or with immune deviation toward the Th1 pathway due to increased levels of interferon- and IL-12. Moreover, treatment with anti- TGF- antibodies did not abrogate oral tolerance. Oral Ag administration was quite effective in suppressing the development of key features of asthma when initiated after primary immunization (Day 0) or after booster (Day 7), but not after challenge (Day 14) when it increased allergic responses. Collectively, our findings show for the first time the beneficial and detrimental effects of oral Ag administration on the development of experimental asthma.

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