The Effects Of Costimulatory Molecule OX40/OX40L On The Pathogenesis Of Allergic Asthma In Mice

Objective We administer the neutralizing anti-OX40L mAb in the BALB/c mice during the sensitization period of asthma to investigate the role of costimulatory molecule OX40/OX40 ligand(OX40L) in the pathogenesis of allergic asthma. Methods Forty-eight female BALB/c mice (6-8week,weight18-20g) were randomly divided into four groups: asthmatic was group A(n=12), anti-OX40L mAb administration was group B(n=12), control mouse IgG administration was group C(n=12), normal saline control was group D(n=12). Mice of group A,B,C were sensitized by i.p. injection of 10% OVA saline soluble 1.0ml on day 0. Mice of group B were injected with 300 ug mouse anti-human OX40LmAb on day 0,3,6,9; Mice of group C were injected with the same dose of control mouse IgG at the same time. On day 14, mice of these three groups were challenged via the airway with aerosolized 5% OVA for 30 min, once a day for seven consecutive days. Saline was administered to the mice of group D in a similar manner. 24h after the final antigen challenge, mice were killed, and BALF was collected from half the mice of each group for counting the total number of BAL cells and the differential cells; IL-4 and INF-γlevels in the BALF were measured by ELISA. Lungs were removed from mice that were not subjected to the bronchial lavage procedure, one of the lungs were stained by HE and PAS to show the inflammation cells infiltration and mucus production, the other lungs were stained by immunohistology to evaluate the expression of OX40L in the lungs. Results (1)The symptom and physical sign were more obvious in group A and C than that of group B, mice of group D have no symptom and physical sign; (2)IL-4 levels in the BALF of mice in group B were reduced than that of group A,C, meanwhile, the INF-γlevels in the BALF of mice in group B were increased than that of group A and C, and the differences were both statistically significant; (3)Total number of cells and the percents of eosinophils,lymphocytes in the BALF were reduced in group B than that of group A,C, and the difference was statistically significant;(4)Lung sections stained by HE showed that the accumulation of inflammation cells around small airway were obviously lower in group B than that of group A,C , the accumulation of inflammation cells in group D was little; PAS staining showed that goblet cell hyperplasia and mucus production were reduced in group B than that of group A and C, there was no goblet cell hyperplasia and mucus production in group D; (5)Immunohistochemical staining of lung sections showed that the expression of OX40L in group A was"++~+++", group B was"+", group C was"++~+++", , group D was"-". Conclusion The costimulatory molecule OX40/OX40L play a critical role in the pathogenesis of allergic asthma. Blocking the costimulatory pathway can inhibit the asthmatic responses, which is contributed to inhibiting the T cell priming and expansion and balancing the Th1/Th2 responses. Blocking the OX40/OX40L interaction appears to be a promising approach of the prevention and therapy of allergic asthma .