ABSTRACT
Objective To determine the CD4+CD25+Foxp3+T regulatory (Treg) cell levels in peripheral blood (PB) of patients with autoimmune diseases (AID) and age-and sex-matched healthy controls. Methods Clinical data and laboratory examinations of AID cases (n=1561) and healthy controls (n=196) were enrolled. The levels of PB Treg cells, other T lymphocyte subsets [total T, CD4+T, CD8+T, T helper1 (Th1), T helper 2 (Th2), and T helper17(Th17) cells] and clinical indicators, laboratory test results were analyzed retro-spectively. Data were analyzed by t test, Mann-Whitney U test,χ2 test and Spearman correlation analysis. Results ①The absolute counts of Treg [22.9(18.31, 36.47) vs 30.24(21.85, 41.34), Z=-3.974, P<0.01], total T (Z=-4.234, P<0.01), CD8+T (Z=-3.801, P<0.01), Th17 (Z=-3.740, P<0.01) cells in PB of patients with AID were significantly lower than those of healthy controls, the levels of CD4+T/Treg (Z=-3.366, P=0.001), Th1/Treg (Z=-3.213, P=0.001) and Th2/Treg (Z=-2.490, P=0.013) in PB of AID patients were higher than those of healthy controls.② The levels of inflammatory indicators were associated with numbers of T lymphocyte subsets. ③ The levels of Treg (Z=-3.624, P<0.01), total T (Z=-2.954, P=0.009), CD4+T (Z=-3.005, P=0.003), Th2 (Z=-1.896, P=0.049) cells in PB of the patients who had been treated with hormones and/or biological or non-biological disease-modifying anti-rheumatic drugs (DMARDs) were significantly lower while the levels of total T/Treg (Z=-2.460, P=0.014), CD8+T/Treg (Z=-3.197, P=0.001) in PB were higher than those of the primary treatment patients. ④ The levels of Treg (Z=-7.105, P<0.01), total T (Z=-2.954, P<0.01), CD4+T (Z=-6.909, P<0.01), Th1 (Z=-4.875, P<0.01), Th2 (Z=-5.751, P<0.01), Th17 (Z=-5.121, P<0.01) cells in PB of the patients with important organs involvement were lower while the ratios of total T/Treg (Z=-4.500, P<0.01), CD8+T/Treg (Z=-5.925, P<0.01) were higher than those non-organ involvement patients. ⑤ The absolute counts levels of T lymphocyte subsets in the AID patients were not significantly correlated with whether there was a single AID and/or multiple AID overlaps. Conclusion The absolute number of peripheral Treg cells decreases significantly in AID, and is correlated with inflammatory indicators. Patients with retreated and organ involve-ment have fewer Treg cells. Our results suggest that Treg cells may play an important role in the pathogenesis of AID.
ABSTRACT
AIM:To construct adenovirus vector expressing mice B7-H1 gene, transfect dendritic cells ( DCs ) , and to study the therapeutic effect of modified DC on thyroid-associated ophthalmopathy ( TAO) in mice. METHODS: We designed and constructed B7-H1 gene adenovirus expression vector, and transfected DCs from mouse bone marrow, tested the phenotype and function of modified DCs, identificated its negative regulation to immune responses. The modified DCs were infected the sicked mice. And then the immunotherapeutic effect of modified DCs to TAO were tested. RESULTS: B7 - H1 gene adenovirus vector was constructed and transfected DCs from bone marrow. The titer of the recombinant adenovirus was 1. 8í109 PFU/mL. B7-H1 gene modified DCs characteristics of regulatory DCs, could inhibit positive immune responses. The inhibition proceeding of TAO into mice infected modified DCs, was obviously prior to the control mice. The gene modified DCs, maybe become the new immunotherapy biological agent to thy TAO. CONCLUSION: We constructed the expression of mouse B7 - H1 gene adenovirus expressed vector successfully, transfected DCs, by vector have properties of regulatory DCs, inhibiting positive immune response and the occurrence and development of thyroid eye disease. Gene modified DCs, reveal potent to the treatment of thyroid eye disease.