A Defect Of CD4~+CD25~+ Regulatory T Cells In Inducing IL-10 Production From CD4~+ T Cells Under CD46 Costimulation In Asthma Patients

Objective:The suppressive cytokine interleukin-10 (IL-10) plays a central role in disease control and clinical therapies of asthma. Complement regulatory factor CD46 is identified as a physiological costimulatory molecule for T cell activation. It can induce IL-10 production in CD4+T cells. Alterations in CD46 costimulation pathway have been proved to be associated with pathological conditions such as multiple sclerosis and hemeodialysis. Whether a similar alteration of this costimulation pathway occurs in allergic asthma is unknown. CD4+CD25+Tregs can suppress the proliferation of effector T cells, and the suppress fuction is defect in asthma patients. They can induce IL-10 secretinon in CD4+CD25- T cells. Our objective is to investigate IL-10 production by CD4+CD25- T cells co-cultured with CD4+CD25+Tregs under CD46 costimulation in asthma and the influence of exogenous glucocorticoid on it.Methods:purified CD4+CD25+Tregs and CD4+CD25- T cells were cultured alone or in the presence or absence of DXM under stimulation with CD3/CD46 or CD3/CD28. Proliferation rates of these cells under both costimulation pathways were assayed by thymidine incorporation, and the levels of IL-10 in supernatants were measured with ELISA. The surface expressions of CD46 molecules in T cells were analyzed with flow cytometry.Results:Levels of IL-10 were higher in undivided CD4+T cells,1:10 co-cultured CD4+CD25+Tregs/CD4+CD25- T cells than those in CD4+CD25- T cells alone either under CD3/CD46 or under CD3/CD28 stimulation both in healthy controls and in asthma patients. IL-10 levels were lower in undivided CD4+T cells and 1:10 co-cultured T cells from asthma patients under stimulation with anti-CD3/CD46 compare to glucocorticoid-treated asthma patients and healthy controls. When treated with DXM, the production of IL-10 in undivided CD4+T cells and 1:10 co-cultured CD4+T cells was normal in asthma patients. The proliferation rates and the surface expression of CD46 molecules in T cells were not different between healthy controls and asthma patients.Conclusion:CD4+CD25+Tregs in asthma patients is deficient in inducing IL-10 production from CD4+CD25- T cells under anti-CD3/CD46 stimulation, and this deficiency is not due to the impaired proliferation or CD46 expression in CD4+T cells from asthma patients. Glucocorticoid treatment is capable of reversing this deficiency. Our findings identified a new functional deficiency of CD4+CD25+T cells in asthma patients. This deficiency may be involved in the pathogenesis of allergic asthma.