| Type 1 diabetes mellitus is characterized by absolute insulin deficiency, abrupt onset of symptoms, proneness to ketosis and dependence on exogenous insulin to sustain life. Complications from diabetes, such as coronary heart disease , retinopathy , nephropathy and stroke are resulting in increasing disability, reduced life expectancy and enormous health cost in virtually every society .Type 1 diabetes mellitus is primarily an autoimmune disease in the classical sense in which the target beta-cell are destroyed by T-lymphocyte-mediated mechanisms. The activation of naive T lymphocytes requires two discrete signals .The first signal is antigen specific and is recognized by T cell receptor .The second signal is nonspecific costimulatory molecules. T cell cannot be activated or even be apoptosis without the costimulatorymolecules. If the second costimulatory molecules express abnormally , it may result in autoimmune diseases including type 1 DM. Activated lymhocytes and macrophages produce and secrete cytokines such as IL-1 TNF- a ^ IFN- Y that can be cytotoxic to beta-cells. This beta-cell toxicity is accompanied by the induction of nitric oxide production, which might be deleterious to the beta-cell itself by mechanisms that resembles apoptosis. Therefore, it is very important to study the abnormal express costimulatory molecules and cytokines in type 1 DM.1. The significance of changes of T lymphocyte subsets and the expression of costimulatory molecules in patients with type 1 diabetes and correlation analysis with islet function.T cell subsets (CD3, CD4, CD8 , CD25) and costimulatory molecules (CD28, CD40, CD40L, 4-lBB,OX-40 and CD80) from 37 patients with type 1 DM were analyzed by immunopheotying and flow-cytometry. The results shows that the percentage of CD3 +T cells, CD4+T cells, and CD4+CD28+Tcells were significantly higher than in normal controls (P<0.01). The percentage of CD8+T cells and CD8+CD28+T cells decreased significantly compared with controls.(P<0.01) .Up-regulated expression of CD28 CD80 4-IBB and HLA-DR were also observed in diabetes group compared with normal controls (P<0.01) . C-P, an indicator of islet function, and INS were bothnegatively correlated with the percentage of CD4+CD28+T cell while positively correlated with that of CD8+CD28+T cell. After treatment with insulin, the imbalance of T cell subsets improved greatly, 4-IBB and HLA-DR were decreased significantly. But some of them were still abnormal compared with controls. Abnormally elevated1 expression of costimulatory molecules CD28, 4-IBB and HLA-DR on peripheral lymphocytes of type 1 diabetes is obviously correlated with the functional changes of the islet.2. The significance of cytokines and their soluble receports in type 1 DM.The serum level of IL-2v sIL-2R, IL-6, sIL-6R (sgp8(K sgp!30) from 20 patients with type 1 DM were investigated by ELISA. The results indicated that the serum levels of IL-2 IL-6x sgp80 were increased significantly than that of healthy controls(p<0.01 ), which were negatively correlated with C-P and INS . The level of sIL-2R decreased remarkably and was positively correlated with islet function . There were no significant changes of sgp130 . The levels of IL-6 sgp8(K sIL-2R were improved partly after 6 months therapy of insulin.In conclusion, the imbalance of T cell subsets > the abnormal expression of CD28,CD80 4-IBB and cytokines IL-2 lL-6 sgp80 were involved inbeta-cell destruction and may play an important role in the pathogenesis and developent of type 1 DM. The costimulatory molecules and IL-2> IL-6> sgpSO may be the useful markers for modulating the immunological state and prognosis of type 1 DM.
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