Reduction and significance of CD4+CD25+Foxp3+ T regulatory cells in the peripheral blood of patients with common autoimmune diseases

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=1 561) 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 ① The 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. Key words: Autoimmune diseases; T-lymphocytes, helper-inducer; T-lymphocyte subsets; Immun-oregulation