Induction of Th2-mediated allergic asthma in a mouse strain highly susceptible to develop th1 responses

GODOY, GJ; SANCHEZ, L; GARCIA, L; MALDONADO, C; MOTRICH, RD; RIVERO, VE

Mar del Plata

Congreso; LIX Reunión Científica Anual de la SAIC ? LXII Reunión Científica Anual de la SAI; 2014

Sociedad Argentina de Investigación Clínica y Sociedad Argentina de Inmunologia

NOD mice are highly susceptible to chronic inflammation disorders mostly mediated by Th1 responses. This increased susceptibility has been thought to be related to defects in regulatory T cells (Tregs). Recent findings evidenced that Tregs subsets are heterogeneous and that different Tregs subsets able to specifically regulate Th1, Th2 and Th17 immune responses would exist.In this work, we developed a model of allergic asthma following established immunization protocols with OVA plus aluminum salts in NOD, C57BL/6 and Balb/c mice. We aimed to analyze if regulatory defects observed in NOD mice were general or just restricted to Th1 responses. After immunization, mice from every strain showed clinical signs and symptoms of allergy when challenged with OVA intranasally. Although increased leukocyte counts in broncoalveolar lavage (BAL) were detected in both immunized NOD and Balb/c mice, the highest levels were seen in Balb/c mice (p<0,05). Broncoalveolar eosinophil recruitment showed to be high, mild and almost null in immunized Balb/c, NOD and C57BL/6 mice, respectively. Moreover, markedly increased, mildly increased and null levels of IL4 and IL5 were respectively detected in BAL from immunized Balb/c, NOD and C57BL/6 mice. Lymph node and spleen mononuclear cell cultures revealed that: a pure Th1 specific immune response is induced in C57BL/6 mice, a mixed Th1/Th2 specific immune response is induced in NOD mice, and a pure Th2 specific immune response is induced in Balb/c mice. Serum OVA-specific IgE levels were positive in all strains, but the highest levels were shown in Balb/c mice (p<0,05).Our results show that although NOD mice mainly induce Th1 responses, they are also able to develop Th2 immune responses. However, these observed Th2 responses developed by NOD mice were much less intense than those shown by Balb/c mice. Although preliminary, our results suggest that NOD mice have impaired immune regulatory capabilities mainly restricted to Th1 responses.