[Effects of immunotherapy on the expression of costimulatory molecules on dendritic cells in a mouse model of asthma].

Objective: To establish a mouse model of ovalbium in (OVA) specific immunotherapy, and to explore the effects of specific immunotherapy on the expression of CD(80) and CD(86) on spleen-derived dendritic cells (DC) in a mouse asthmatic model.

Methods: A hundred and twenty BALB/c mice were randomly divided into three groups, with 40 mice each. The asthma model (group A) was established by intraperitoneal injection of 10 microg OVA and 1% OVA aerosol challenges. Consecutive subcutaneous injection of 1 mg OVA in the dorsal aspect of the foot was then given to establish the model of OVA specific immunotherapy (group B), while PBS (0.01 mol/L) was given in group C to serve as the control. The pathological changes of lung tissues were studied by HE stain. The serum OVA-specific IgE level, and IL-2 and IL-4 production in the splenic T cells were determined by enzyme-linked immunosorbent assay (ELISA). The expression of CD(80) and CD(86) on DC, which were isolated from the spleen, were detected by fluorescein-activated cell sorter. (3)H-thymidine ((3)H-TdR) incorporation assay was used to determine the response of splenic T and the secretion of interleukin-4 (IL-4) and IL-5 was assayed with the use of ELISA after coculture of T cells with DC.

Results: (1) The infiltration of eosinophils and lymphocytes within epithelium and lamina propria was present in group B, but was milder than that in group A. The absorbance at 490 nm (A(490)) of serum specific IgE in group A 712 +/- 129, was more than that in group C (20 +/- 13, P < 0.05), but there was no significant difference between group B (124 +/- 59, P > 0.05) and C. The production of IL-2 by splenic T cells in group B (8 +/- 3) pg/ml was less than that in group A [(22 +/- 8) pg/ml, P < 0.05], but there was no significant difference between group B and group C [(6 +/- 4) pg/ml, P > 0.05]. The production of IL-4 by splenic T cells in group B (8.4 +/- 4.3) pg/ml was less than that of group A [(32.4 +/- 12.1) pg/ml, P < 0.05], but there was no significant difference between group B and group C [(5.1 +/- 1.1) pg/ml, P > 0.05]. (2) The expression of CD(86) on splenic DC cells from group B (58.23%) was significantly lower than that from group A (77.59%) and group C (77.84%), while the expressions of CD(80) in group A (96.98%) and group B (95.63%) were higher than that in group C (77.37%). (3) When untreated T cells were cocultured with DC from the individual groups and stimulated by OVA, the secretion of IL-4 from T cells in group B [(10.8 +/- 2.3) pg/ml] was significantly lower than that in group A [(17.3 +/- 4.7) pg/ml, P < 0.05], but there was no significant difference when compared to group C [(5.7 +/- 2.7) pg/ml, P > 0.05], and the secretion of IL-5 from T cells in group B [(18.8 +/- 3.8) pg/ml] was significantly lower than that in group A [(35.7 +/- 7.9) pg/ml, P < 0.05], but there was no significant difference when compared to group C [(11.0 +/- 2.2) pg/ml, P > 0.05]. When untreated T cells were cocultured with DC from the individual groups and stimulated by OVA, the stimulating index of T cells in group B (3.8 +/- 0.7) was significantly lower than that in group A (11.5 +/- 3.2, P < 0.05), but there was no significant difference when compared to group C (5.8 +/- 1.5, P > 0.05).

Conclusions: A mouse model of asthma-specific immunotherapy was successfully established. Downregulation of CD(86) on the surface of DC might be the underlying mechanisms by which specific immunotherapy promotes Th1 to Th2 polarization and induces T cell anergy.