Pretransplant donor peripheral blood mononuclear cells infusion induces transplantation tolerance by generating regulatory T cells

BACKGROUND: It was suggested that maintenance of tolerance to organ transplantation may depend on the formation of T regulatory cells. METHODS: Lewis (LW) rats were made tolerant to a Brown Norway kidney by pretransplant donor peripheral blood mononuclear cells (PBMC) infusion. At greater than 90 days after transplantation, lymph node cells (LN) and graft-infiltrating leukocytes (GIL) alloreactivity was tested in mixed lymphocyte reaction (MLR), coculture, and transwell experiments. GIL phenotype was analyzed by FACS. mRNA expression of cytokines and other markers was analyzed on CD4+ T cells from LN. The tolerogenic potential of tolerant cells in vivo was evaluated by adoptive transfer. RESULTS: Tolerant LN cells showed a reduced proliferation against donor stimulators but a normal anti-third-party alloreactivity. In coculture, these cells inhibited antidonor but not antithird-party reactivity of na?ve LN cells. Interleukin (IL)-10 and FasL mRNA expression was up-regulated in tolerant CD4+ T cells, but an anti-IL-10 monoclonal antibody (mAb) only partially reversed their inhibitory effect. Immunoregulatory activity was concentrated in the CD4+ CD25+ T-cell subset. In a transwell system, tolerant T cells inhibited a na?ve MLR to a lesser extent than in a standard coculture. Regulatory cells transferred tolerance after infusion into na?ve LW recipients. CD4+ T cells isolated from tolerized grafts were hyporesponsive to donor stimulators and suppressed a na?ve MLR against donor antigens. CONCLUSIONS: Donor-specific regulatory T cells play a role in tolerance induction by donor PBMC infusion. Regulatory activity is concentrated in the CD4+ CD25+ subset and requires cell-to-cell contact. Regulatory CD4+ T cells accumulate in tolerized kidney grafts where they could exert a protective function against host immune response.     

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

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Moderately Hypofractionated Helical IMRT,FDG–PET/CT-guided,for Progressive Malignant Pleural Mesothelioma in Patients With Intact Lungs

Introduction

The objective of this study was to present the outcomes of moderately hypofractionated helical intensity-modulated radiation therapy (HT) with/without simultaneous integrated boost (SIB) on fluorodeoxyglucose-positron emission tomography (FDG-PET) positive areas (gross tumor volume [GTV]-PET) for patients with progressive malignant pleural mesothelioma (MPM) after previous treatments.

Expression of anti-heterogenous nuclear ribonucleoprotein (anti-hnRNP) in limited systemic sclerosis patients: Relation to radiographic findings of the hand

Background

Systemic sclerosis (SSc) is an autoimmune connective tissue disease with vascular, fibrotic and immune changes of skin and some internal organs. Anti-heterogeneous nuclear ribonucleoproteins (anti-hnRNP) were found in SSc patients.

Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy

Subclinical hypothyroidism (sHT) is associated with enhanced cardiovascular risk. To test the hypothesis that patients with sHT are characterized by endothelial dysfunction and impaired nitric oxide (NO) availability, in 14 patients [serum cholesterol, 218 +/- 41 mg/dl (5.6 +/- 0.9 mM)] and 28 euthyroid subjects, subdivided into groups A and B [serum cholesterol, 170 +/- 19 mg/dl (4.4 +/- 0.5 mM) and 217 +/- 21 mg/dl (5.6 +/- 0.5 mM), respectively], we studied the forearm blood flow (strain-gauge plethysmography) response to intrabrachial acetylcholine, an endothelium-dependent vasodilator, at baseline and during infusion of N(G)-monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor. Response to sodium nitroprusside and minimal forearm vascular resistances were also evaluated. In sHT patients, vasodilation to acetylcholine was reduced, compared with group B (+358 +/- 29% vs. +503 +/- 19%, P = 0.0003) and group A (663 +/- 65%, P = 0.02 vs. group B and P = 0.0002 vs. sHT). L-NMMA blunted the vasodilation to acetylcholine in groups A and B (49.1 +/- 6.3% and 42.7 +/- 5.5% maximal forearm blood flow reduction, respectively, P < 0.0001 vs. acetylcholine), whereas it was ineffective in sHT patients (12.8 +/- 2.5%). Response to sodium nitroprusside and minimal vascular resistances were similar. In sHT (n = 9) patients, 6 months of euthyroidism by levothyroxine replacement increased acetylcholine-vasodilation and restored L-NMMA inhibition. Patients with sHT are characterized by endothelial dysfunction resulting from a reduction in NO availability, an alteration partially independent of dyslipidemia and reversed by levothyroxine supplementation.     

Impact of carboxylation and hydrolysis functionalisations on the anti-oil staining behaviour of textiles grafted with poly(N-isopropylacrylamide) hydrogel

Novel hydrogel-modified textiles have been prepared through photografting poly(N-isopropylacrylamide) (PNIPAAm) onto pristine and functionalised polyethylene terephthalate (PET) surfaces. In this work, two types of functionalisation, carboxylation (CPET) and hydrolysis (HPET), were performed to scrutinise the hydrogel grafting efficiency. Basic characterisation of the pristine, functionalised and grafted textiles was carried out via fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and field emission scanning electron microscopy (FESEM) analyses. Then, the functional characteristics of these samples were determined based on the oil staining performance. Functionalisation of the PET textiles via hydrolysis and carboxylation gives rise to different chemical reactivity and interactions on the PET surface. Impressively, the surface formed via hydrolysis functionalisation of PET was found to be more efficient compared to that formed via carboxylation, and the untreated one. The HPET surface was remarkably more hydrophilised and rougher than both the UPET and CPET surfaces. The accessibility of the –OH groups for hydrogen abstraction from HPET has a great impact on the hydrogel grafting onto the HPET surface. All the grafted textiles (PNIPAAm-g-UPET, PNIPAAm-g-CPET and PNIPAAm-g-HPET) demonstrated anti-oil staining behaviour at 27 °C. In particular, PNIPAAm-g-HPET textiles with a high degree of grafting (DG) exhibited the fastest rate for oil to de-stain from the surface. Moreover, the reversible transition of PNIPAAm hydrogels around the lower critical solution temperature (LCST) ∼ 32 °C from hydrophilic to hydrophobic generates switchable surfaces of the textiles with regard to the oil wettability. Specifically, PNIPAAm-g-HPET textiles also displayed the highest degree of wettability switching as a result of having the highest DG. Taken together, the PNIPAAm hydrogels grafted onto PET textiles were significantly enhanced though hydrolysis functionalisation and possessed excellent switchable surfaces toward oil-staining, having great potential to be used for applications in oil and water separation as well as smart textiles.

Functionalisation, especially via hydrolysis, has created efficient PNIPAAm hydrogels grafted onto PET textiles with superior anti-oil staining performance.