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Borducchi E. Use and limitations of peripheral tolerance in experimental model of asthma [Thesis, PhD Programme in Imunollogy]. São Paulo: Instituto de Ciências Biomédicas da Universidade de São Paulo; 2009. Asthma is a chronic lung disease associated with eosinphils, broncus hyperactivity, mucus and elevated levels of IgE. It is known that mucosal administration of soluble proteins, before the sensitization with the same protein, leads to a specific state of hyporesponsiveness, a process known as mucosal tolerance. In this work we studied the effect of LPS inhalation during the induction of ovalbumin (OVA) nasal tolerance. The majority of murine models of asthma used OVA as allergen, although its prevalence as a cause of asthma is low. Thus, we also used, in this study, Blomia tropicalis (Bt) allergens that are more common in asthmatic patients. Intrinsic features of the allergens presented in the mite extract block the nasal tolerance establishment. Experimental data indicates that tolerance towards an Ag can promote tolerance to another not related Ag (cross-tolerance). Therefore, we evaluated if OVA or hen-egg white lisozyme (HEL) tolerance could result in crosstolerance to the Bt allergen. Our data showed that administration of LPS during induction of nasal tolerance to OVA prevents the establishment of this tolerance, resulting in neutrophil and mononuclear cells migration to the lungs and IgG2a production, decreased levels of IgE and increased anaphylactic IgG1. Indeed, the LPS administration during the induction of tolerance induces a peculiar allergic state. In relation to cross-tolerance, we verify that nasal tolerance to HEL or OVA is not capable in induce cross-tolerance towards responses against the Bt extract. On the other hand, OVA oral tolerance is absolutely able to induce cross-tolerance to responses against Bt, with inhibition of both IgE and anaphylactic IgG1 Bt-specific antibodies. The cross tolerance occur only if the tolerated antigen (OVA) is presented together with Bt allergen. Finally, we verified that in allergen sensitized mice the induction of oral tolerance with OVA does not lead to cross-tolerance.

Uso e limitações da tolerância imunológica periférica em modelo de asma experimental