Abnormal Expansion Of CD4~+CD28~-T Cell Subsets And Its Clinical Significance In Children Bronchial Asthma

Bronchial asthma is a chronic inflammatory disease involved by many inflammatory cells such as eosinophils, mast cells, T cells and cellular components. T cell is the key regulatory cell. The over-activation of T cells and dysfunction of T help cells (Th1/Th2) are the important mechanism in asthma. CD4+CD28- T Lymphocytes are seldom seen in peripheral blood of healthy persons. But they are thought to be auto-reaction T cells because of their abnormal expression in peripheral blood of immune inflammatory disease patients. The function and mechanism of CD4+CD28- T cell subsets in hypersensitivity disease such as asthma are necessary to be investigated. In this study we manifest the mechanism of CD4+CD28- T Lymphocytes in the development of asthma through detecting the CD4+CD28- T Lymphocytes expression in peripheral blood of asthma children and analyzing the correlation with clinical characters, IgE and cytokines in serum.PartⅠ: Abnormal expansion of CD4+CD28- T lymphocytes in peripheral blood of children with asthma and its clinical correlationObjective: To detect the expansion of CD4+CD28-T lymphocytes in peripheral blood of children with asthma, analysis the correlation of CD4+CD28-T lymphocytes expansion and clinical features of asthma children.Methods: The expansion of CD4+CD28-T lymphocytes was detected in 57 asthma children and 29 healthy children blood by immunofluorescence staining and Flow Cytometry. Then we analyze the relationship between the CD4+CD28-T lymphocytes percentage and the severity of the disease, the frequency in one year, allergy history, family history etc. At the same time we measured serum IgE and analyzed the correlation with the CD4+CD28- lymphocytes percentage.Results: The percentage of CD4+CD28-T lymphocytes in asthma children was remarkably higher than healthy children in control group. There were significances in statistics (P<0.05). The percentage of CD4+CD28-T lymphocytes in severe asthma was significantly higher than mild ones (P<0.05). If the children got the disease frequently in one year, the percentage was also significantly higher (P<0.05), if the children had the history of the allergy, the percentage was significantly higher than non allergic patients. However, the percentage in children with family history was a little higher than non family history children. There were no statistic significance (P>0.05). The percentage of CD4+CD28-T cells in children received regular treatment was significantly higher than children not received standard treatment (P<0.05). The percentage of peripheral blood CD4+CD28-T lymphocytes had positive correlation with serum lgE in asthma children. (P<0.01, r=0.390).Conclusion: The expansion of CD4+CD28-T lymphocytes in peripheral blood of patients with asthma was abnormal increased and it was correlated with the clinical characterizations in asthma. The percentage was positively correlated with the serum IgE levels. CD4+CD28-T lymphocytes are involved in the asthma immune pathologic response.PartⅡ: The change pattern of the CD4+CD28- T lymphocytes expansion at different stages of treatment and its correlation with serum cytokines in bronchial asthma childrenObjective:To analyze the change pattern of CD4+CD28-T lymphocytes expansion, CD4+T lymphocytes expansion and serum cytokines secretion in peripheral blood, investigate the immune function and airway inflammation changes and analyze its clinical significance at different stages of treatment in asthma children. Methods: After received the appropriate treatment of budesonide inhalation in the acute stage of 27 bronchial asthma children, the PEF level was recovered to normal level. To analyze serum cytokines at different stages of treatment by ELISA assay in 21 patients and 29 health children. The data were collected before the treatment and one week, two weeks, one month, three months, and six months after the treatment. To detect the percentage of peripheral blood CD4+T lymphocytes and CD4+CD28-T lymphocytes in asthma children by flow cytometry, then to undertake statistic analysis.Results: 1) There was a significantly downward tendency of IL-4 and IL-5 secretion in bronchial asthma children serum at the different stage of treatment (P<0.05). Compare the health control group, IL-4 and IL-5 secretion were significantly higher in other groups (P<0.05). But IFN-γwas significantly increased in bronchial asthma children serum at the different stage of treatment (P<0.05). Compare the health control group, IFN-γsecretion was significantly reduced in other groups (P<0.05). 2) The percentage of CD4+T lymphocytes is gradually lowered in the blood of children received treatment. Between the patients be treated one week, two weeks and a month and before the treatment, the percentage of CD4+T lymphocyte decreased remarkably (P<0.05). And compare with the health control group, the percentage was significantly increased in each group (P<0.05). However, the percentage of CD4+T lymphocytes is not decreased compared with health group at one month, three months and six months after treatment(P>0.05). The percentage of CD4+CD28-T lymphocytes was also decreased, each group was decreased remarkably compared with the last group at six months after treatment (P<0.05). The amount in each group is higher than health group (P<0.05). 3)The serum IL-4 level is correlated with CD4+T lymphocyte whenever before treatment, at one week or two weeks after treatment(P<0.05). At six months after treatment, CD4+CD28- T lymphocytes were positively correlated with the IL-4(P<0.05).Conclusion:1) The airway inflammation in bronchial asthma was gradually suppressed in children at six months after treatment, but it was still enhanced than healthy persons, so it must put emphasis on the treatment in remission duration. 2) CD4+CD28-T lymphocytes were closely correlated with the treatment and prognosis of bronchial asthma.