Hungarian Immunology

[Regulatory T cells in mixed connective tissue disease]

BARÁTH Sándor, ALEKSZA Magdolna, SZEGEDI Andrea, SIPKA Sándor, SZEGEDI Gyula, BODOLAY Edit

OCTOBER 10, 2005

Hungarian Immunology - 2005;4(03-04)

[INTRODUCTION - CD4+/CD25+high suppressor and IL-10 producing CD4+ regulatory T (IL-10 Treg) cells were investigated in the peripheral blood of 48 patients with mixed connective tissue disease (MCTD). Seventeen patients were in active and 31 patients in inactive state. PATIENTS AND METHODS - Measurement of the number of CD4+CD25+high suppressor and IL-10 Treg cells was carried out by flow cytometry. RESULTS - The absolute number and percent of CD4+CD25+high T cells decreased in MCTD patients compared to the healthy controls. The number of CD4+CD25+high Treg cells was lower in 17 active MCTD patients than in the inactive patients. The percent and absolute number of IL-10 Treg was elevated in the peripheral blood of patients with MCTD compared to the healthy controls. Corticosteroid and immunosuppressive drugs moved the number of regulatory T cells (CD4+CD25+high and IL-10 Treg cells) towards the normal value. CONCLUSIONS - Our results show that the decrease in the number of CD4+CD25+high T cells could play a key role in the immunoregulatory disturbance in MCTD. Elevation in the number of IL-10 Treg cells might be a compensatory mechanism to retain the balance of proinflammatory and anti-inflammatory cytokines.]



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[Aims - In this study we investigated whether calorie restriction or redundant food intake influences the function of regulatory T cells (Tregs), and their main regulators (dendritic cells and macrophages), or the targets of Tregs, CD4+ lymphocytes. Patients and methods - We investigated 11 white adolescents (10 girls and 1 boy) with anorexia nervosa, 12 obes adolescents and 10 healthy controlls. With flow cytometry we determined the prevalence of Tregs, myeloid and plasmacytoid dendritic cells. We applied intracellular staining to investigate TNF-alpha and IL-12 production of macrophages, moreover IL-2, IL-4, and IFN-gamma production of CD4+ cells. We also determined calcium flux kinetics upon activation in CD4+ cells. Results - We did not find any difference between obese, anorectic and control individuals in the prevalence of Tregs, dendritic cells, TNF-alpha and IL-12 positive macrophages, IL-4 and IFN-gamma positive CD4+ lymphocytes. We found that the prevalence of IL-2 positive lymphocytes after activation was lower in anorectic than in control subjects [median (range): 11.50 (7.60-15.30) vs. 13.50 (12.00-22.00), p=0.023], and in obese patients, too [12.50 (8.50-15.50) vs. 13.50 (12.00-22.00), p=0.028]. IFN-gamma/IL-4 ratio in CD4+ cells was higher in obese patients compared with control (p=0.046). The calcium flux characteristics of lymphocytes upon activation differed markedly in anorectic and healthy subjects as maximal calcium levels developed later in anorectic patients [86 (45- 232) vs. 215 (59-235) second, p<0.05]. We also tested the association between lymphocyte activation parameters and patients' clinical status, but did not find any association between the variables. Discussion - Our results suggest that the antigen presenting cell - regulatory T cell - CD4+ lymphocyte axis might be affected by calorie and nutritional disturbances, further studies are needed to elucidate the underlying processes.]

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[INTRODUCTION - Mixed connective tissue disease (MCTD) is an inflammatory autoimmune disease with multiple organ involvement. Immune- inflammatory processes play a crucial role in the pathogenesis of atherosclerosis. The connection between inflammatory parameters and atherosclerosis in MCTD has not yet been studied. Lipid abnormality is an important risk factor of atherosclerosis. Among the lipids, HDL is protective, which is in part due to the antioxidant effect of paraoxonase. In this paper, the lipid profiles and paraoxonase activities of MCTD patients were studied and the factors causing abnormalities were investigated. PATIENTS AND METHODS - Thirty-seven patients with MCTD, who had not taken any lipid lowering drugs in the past 2 months, were enrolled in the study. Thirty healthy individuals served as controls. At the time of the study the mean age of the MCTD patients was 51.2 ± 9.5 years, and the mean disease duration was 11.0 ± 7.2 years. Paraoxonase activity was determined by spectrophotometry, lipid profiles were determined by a Cobas Integra 700 Analyser, the von Willebrand factor antigen (vWFAg) was measured by turbidimetry in platelet-poor plasma and the thrombomodulin and anti-endothelial cell antibody (AECA) measurements were carried out by ELISA methods. RESULTS - Paraoxonase activity in the MCTD patients was lower than in the control population (118.5 ± 64.6 U/l vs. 188.0 ± 77.6, p<0.001). The arylesterase activity was also significantly lower in the patients (p<0.001). The reduction of paraoxonase activity was in correlation with the age of the patients, the duration of the disease and with vascular (eye, cardiac, cerebral) disorders. The total cholesterol and triglicerid levels of the patients were significantly increased compared to the control group, while in the apoA1 levels a significant reduction was seen. A very strong correlation was observed between the reduction of paraoxonase activity and the increase of endothelial cell activation markers (thrombomodulin, vWFAg, AECA). There was no difference in the values of patients with or without corticosteroid treatment. CONCLUSIONS - The results suggest that in MCTD there is an increased risk for atherosclerosis. Apart from an elevated cholesterol and triglicerid level, a reduced paraoxonase level and activity may also play a role in the development of atherosclerosis,. Therefore, in patients with MCTD, due to the increased oxidative processes and the impaired elimination of free radicals, a sustained damage to the endothelial cells occurs, which is indicated by increased levels of thrombomodulin, vWFAg, and anti-endothelial antibody.]

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