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OBJECTIVEType 1 diabetes is a condition in which pancreatic islets are destroyed by self-reactive T cells. The process is facilitated by deficits in the number and suppressive activity of regulatory T cells (Tregs). Here, we show for the first time that the infusion of autologous Tregs prolongs remission in recently diagnosed type 1 diabetes in children.RESEARCH DESIGN AND METHODSWe have administered Tregs in 10 type 1 diabetic children (aged 8–16 years) within 2 months since diagnosis. In total, 4 patients received 10 × 106 Tregs/kg body wt, and the remaining 6 patients received 20 × 106 Tregs/kg body wt. The preparation consisted of sorted autologous CD3+CD4+CD25highCD127− Tregs expanded under good manufacturing practice conditions.RESULTSNo toxicity of the therapy was noted. A significant increase in the percentage of Tregs in the peripheral blood has been observed since the day of infusion. These patients were followed along with matched type 1 diabetic patients not treated with Tregs. Half a year after type 1 diabetes onset (4–5 months after Tregs infusion), 8 patients treated with Tregs still required <0.5 UI/kg body wt of insulin daily, with 2 patients out of insulin completely, whereas the remission was over in the nontreated group. In addition, plasma C-peptide levels were significantly higher in the treated group as compared with those not treated.CONCLUSIONSThis study shows that the administration of Tregs is safe and tolerable in children with recent-onset type 1 diabetes.

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The results of our study show that intranasal, similarly to transdermal, E2 administration does not increase serum CRP levels in postmenopausal women. They also support the hypothesis that CRP increase during oral estrogen treatment is not mediated by the enhancement of interleukin-6 production by the immune cells but is rather caused by the hepatic first-pass metabolism effect.

Monocytes are short-lived cells and undergo spontaneous apoptosis every day. Inflammatory responses may induce dramatic up-regulation of monocyte survival and differentiation. When monocytes are recruited to an area of infection they may differentiate into macrophages. In different microenvironments macrophages polarize into two types. The M1 or classically activated macrophages are characterized by the high ability to produce pro-inflammatory cytokines and the production of NO through the induced synthesis of iNOS. The M2 or alternatively activated macrophages are divided into 3 subtypes, M2 a, b and c, and they have anti-inflammatory properties. Mediators of M1 macrophage TLR-dependent polarization include transcription factors such as NF-κB, AP-1, PU.1, CCAAT/enhancer-binding protein α (C/EBP-α), STAT1 as well as interferon regulatory factor 5 (IRF5), while the transcription factors which promote M2 activation include IRF4, C/EBP-β, Krüppel-like factor 4 (KLF4), STAT6 and PPARγ receptor.