The Change Of Il-10, Tgf-β1 And Cd4~+cd25~+ T Cells During Specific Immunotherapy For Children With Allergic Asthma

Background and ObjectiveThe allergic asthma is a kind of chronic respiratory passage disease,whose machamisms remain unclear.It has been accepted for a long time that this allergic disease is related to the imbalance of Th1/Th2 and the predominance of Th2 cells.But this theory can not explain all the mechanisms.Many researches have indicated that the inhibitory cytokines IL-10,TGF-β1 and CD4⁺CD25⁺ T cells may play an important role in the development of asthma.These factors have been paid attention to extensively now.IL-10 and TGF-β1 are key immunosuppressive cytokines.IL-10 may repress the inflammation of the respiratory passage and the development of asthma in the end through the following methods:inhibiting T cells proliferation and secreting cytokines directly,inducing the T cell anergy,repressing APC to supress T cell response indirectly,inhibiting secreting specific IgE but promoting the synthesis of IgG4.The effect of TGF-β1 in asthma is very complicated,it is still debated now. Most people think that the local TGF-β1 promotes the development of inflammation but it all over the body inhibites the inflammation.CD4⁺CD25⁺ T cells include CD4⁺CD25⁺ regulatory T cells(Treg) and activated CD4⁺ T cells,they are mixture of many kinds of cells.The CD4⁺CD25⁺ Treg which is a immunoregulatory cell is a hot spot of recent researches.It supresses the development of immune diseases by regulating periphery immunological tolerance.It not only can repress Th1 cell respond, but can also repress Th2 cell respond,and the latter effect is stronger.We can consider that CD4⁺CD25⁺ Treg can regulate the balance of Th1/Th2 and inhibit the differentiation of Th2 cells to enhance the activity of Th1 cells,prevent and cure allergic disease.Following with the further study,we find only CD4⁺CD25^high Treg plays immunoregulatory role in people.The chief therapy of asthma is antiinflammation and spasmolysis for a long time.The allergen specific immunotherapy(SIT) may be the only etiotropic treatment which can change the course of disease.But its merchanisms remain unclear.So,the current study was designed to investigate the machanisms of SIT and find new therapy through detecting the change of IL-10,TGF-β1 and CD4⁺CD25⁺ T cells and the efficiency during specific immunotherapy for children with allergic asthma.MethodsThe forty patients with allergic asthma(24 boys and 16 girls) were from department of pediatics of the first affiliated hospital of Zhengzhou Univercity.The mean age was 8.42 years old.All the patients had the typical symptoms and medical history of asthma,fullfilled the diagnostic criteria of asthma.Their skin test of dust mites was positive and they undertook the SIT(ALK,Danmark).In this study,the patients were divided into three groups:pre-SIT,post-SIT for 1 year and post-SIT for 2 years.The peripheral venous blood was obtained respectively at the pre-SIT, post-SIT for 1 year and post-SIT for 2 years time.The cytokines of IL-10 and TGF-β1 mRNA in PBMCs were detected by SYBR Green I real-time RT-PCR;The percentages of CD4⁺CD25⁺ T cells and CD4⁺CD25^high T cells in peripheral blood CD4⁺ T cells were evaluated by flow cytometry.At the same time,the clinical effects were detected.In the end,the results were dealt with the statistical software. ResultsWith the progression of SIT,we found that the expression of IL-10 mRNA in post-SIT for 1 year group was 3.29-fold than that in pre-SIT group,but it reduced in post-SIT for 2 years group significantly,was 1.01-fold than that in pre-SIT group.The expression of TGF-β1 mRNA had no significant change during the SIT.The percentage of CD4⁺CD25⁺ T cells in periphery blood CD4⁺ T cells did not change remarkably during the SIT(P＞0.05);The percentage of CD4⁺CD25^high T cells in peripheral blood CD4⁺ T cells in post-SIT for 1 year group was much higher than that in pre-SIT group(P＜0.05),and it retained in high level in post-SIT for 2 years group. The clinical symptom were alleviated.ConclusionsIn conclusion,the SIT is efficient for the patients with allergic asthma;With the progression of SIT,the expression of IL-10 mRNA and the percentage of CD4⁺CD25^high T cells in peripheral blood CD4⁺ T cells increased,IL-10 and CD4⁺CD25^high T cells could play a critical role in the SIT.