[The effects of dendritic cells overexpressing Serrate1 on the differentiation of CD4(+)CD25(+) T cells in asthmatic mice].

OBJECTIVE: To observe the effects of dendritic cells (DCs) overexpressing Serrate1 on the differentiation of CD(4)(+)CD(25)(+) T cells and the production of inhibitory cytokines in asthmatic mice. METHODS: Asthma mouse model was established by the routine method. After intravenous injection of the DCs transfected with Serrate1 into the naïve mice, the airway and lung inflammation was observed and the count of CD(4)(+)CD(25)(+) T cells delivered from the spleen and the percentage accounting for CD(4)(+)T cells were measured by flow cytometry. The expression of IL-10, transforming growth factor (TGF)beta1, and cytologic T-lymphocyte-associated antigen (CTLA)-4 mRNA of CD(4)(+) T cells were detected by RT-PCR. RESULTS: Compared with the non-transfected group, the airway inflammation of asthmatic mice injected the DCs transfected with Serrate1 reduced significantly, the number of CD(4)(+)CD(25)(+) T cells delivered from the spleen and the percentage accounting for CD(4)(+) T cells and the expression of IL-10, TGFbeta1, and CTLA-4 mRNA of CD(4)(+) T increased. CONCLUSIONS: DCs overexpressing Serrate1 could induce the differentiation of the CD(4)(+)CD(25)(+) T cells and increase the production of inhibitory cytokines in asthma in vivo, indicating that Notch1/Serrate1 signal pathway of DCs plays an important role in the induction of immune tolerance of T cells to allergens.

[Effects and mechanism of CD4+ CD25+ T cells on the airway inflammation of asthmatic mice].

OBJECTIVE: To investigate the effects and mechanism of CD(4)(+) CD(25)(+) T cells on the airway inflammation of asthmatic mice. METHODS: Sixty mice were divided into 3 groups (20 in each group) including group A [ovalbumin (OVA) sensitized/challenged mice], group B (saline sensitized/challenged mice), group C [CD(25)(+) T cells deleted by anti-CD(25)(+) and OVA sensitized/challenged mice]. Mice of A group were sensitized on days 1 and 13 by OVA and challenged from days 21 to 29 by 2% OVA 10 ml repeatedly to establish a murine model of asthma characterized by airway inflammation. The mice of group B were treated by saline 10 ml. The mice of group C were treated by the same method of group A after deletion of the CD(25)(+) T cells by anti-mouse CD(25)(+) monoclonal antibody (McAb). Lymphocytes were separated from the spleen of the three groups and the number of T cells were calculated by Fluorescence Activated Cell Sorter (FACS). The CD(4)(+) T cells were purified and the expression of interleukin-10 (IL-10), transforming growth factor-beta(1) (TGF-beta(1)) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) mRNA were analyzed by the method of reverse transcriptase-polymerase chain reaction (RT-PCR). The airway inflammatory indices were detected by hematoxylin and eosin (HE) staining. RESULTS: In repeatedly OVA-challenged mice (group A), the ratio of CD(4)(+) CD(25)(+) T cells to CD(4)(+) T cells decreased significantly [(3.10 +/- 0.03)%] as compared with group B [(9.60 +/- 0.04)%, P < 0.01]. The expression of IL-10, CTLA-4 mRNA and TGF-beta(1) mRNA of OVA-challenged mice (group A) decreased significantly (0.250 +/- 0.040 vs 0.29 +/- 0.03, 0.28 +/- 0.06 vs 0.480 +/- 0.080, 0.47 +/- 0.05 vs 0.50 +/- 0.03, all P < 0.01). The expression of IL-10, CTLA-4 mRNA and TGF-beta(1) mRNA of the mice treated by anti-CD(25)(+) McAb (group C) decreased as compared with groups A and B (0.080 +/- 0.020, 0.11 +/- 0.04, 0.12 +/- 0.05, P < 0.01). The inflammation in the lungs of mice with depleted CD(4)(+) CD(25)(+) T cells by anti-CD(25)(+) McAb was more marked than that in the OVA-challenged and control group mice. CONCLUSION: The polarization of CD(4)(+) CD(25)(+) T cells in asthmatic mice decreased significantly, which may play an important role in the pathogenesis of asthma.

Comparison of inhaled corticosteroid combined with theophylline and double-dose inhaled corticosteroid in moderate to severe asthma.

OBJECTIVE: Recent studies have found that theophylline exerts anti-inflammatory and immunomodulatory effects. This study was performed to compare the efficacy of inhaled corticosteroids (ICS) combined with slow-release theophylline (SRT) with that of double-dose ICS in asthma control, anti-inflammatory activity and safety. METHODOLOGY: In a randomized, open, parallel, control trial, 41 patients with asthma were randomly treated with either beclomethasone dipropionate 500 microg b.i.d. (BDP group) or a combination of BDP 250 microg b.i.d and SRT 0.2 g b.i.d. (SRT/BDP group) for 6 weeks. At the start and at the end of treatment, lung function testing and sputum induction were performed, and plasma cortisol levels were measured. Sputum was analyzed for cell differential counts and the interleukin (IL)-5 level. Patients kept a record of peak expiratory flow (PEF), symptom score, and beta2-agonist use. RESULTS: Significant increases in the morning and the evening PEF and FEV1 were observed (P < 0.05), together with an obvious reduction in symptom score and beta2-agonist use (P < 0.01). Significant decreases in the percentage eosinophils and IL-5 level in induced sputum also occurred (P < 0.05). However, there was no difference between the two groups for all these parameters. There was no significant change in the plasma cortisol level for either group. CONCLUSIONS: Both ICS combined with SRT and double-dose ICS had the same effect on asthma control, improving symptoms and ameliorating lung function. Both therapies had similar anti-airway inflammatory effects and therapeutic safety. Combining SRT with ICS may allow a reduction in ICS dose when treating asthma.