ABSTRACT
The goal of this study was to identify immunological markers for use in antigen-specific assays that predict long-term survival after renal allograft and distinguish stable-functioning (SP) patients from poorly functioning (PP) patients. For this prospective study, 20 patients were enrolled. Eight SP and six PP patients were enrolled in this study. Serum cytokine/chemokine levels were analyzed by the Luminex multiplex assay. To detect indirect alloreactive T cells, we performed indirect mixed lymphocyte reaction using donor-antigen-pulsed autologous dendritic cells as stimulators. Serum induced protein-10 levels were significantly higher in the serum of PP patients, whereas sCD40L levels were higher in SP patients. The PP patients had significantly higher numbers of donor-specific CD4(+)CD43(high)CD45RO(+) T cells after indirect allostimulation, whereas this cell population was unchanged in SP patients. The donor-specific CD4(+)CD43(high)CD45RO(+) T cells had the effector memory T cell phenotype. Prospectively, we studied whether these cells influence graft outcome and found that their strong proliferation in pre-transplant patients is related to a poorly functioning graft. Indirectly allostimulated CD4(+)CD43(high)CD45RO(+) T cells may not only contribute to chronic allograft nephropathy development but may also have a role in the progression of acute rejection. Thus, these cells may have potential use as immune-monitoring markers in a noninvasive in vitro assay that predicts graft outcome.
Subject(s)
Allografts , CD4-Positive T-Lymphocytes/immunology , Graft Rejection/pathology , Kidney Transplantation , Leukocyte Common Antigens/analysis , Leukosialin/analysis , T-Lymphocyte Subsets/immunology , Adult , Aged , Biomarkers/analysis , CD4-Positive T-Lymphocytes/chemistry , Cytokines/blood , Female , Graft Rejection/diagnosis , Humans , Male , Middle Aged , Prospective Studies , T-Lymphocyte Subsets/chemistryABSTRACT
Asymmetric dimethylarginine (ADMA) is a risk factor of cardiovascular diseases. alpha-Lipoic acid (ALA) was shown to improve vascular dysfunction, and to decrease plasma ADMA level. In this study, we investigated whether ALA activates dimethylarginine dimethylaminohydrolase (DDAH), the metabolizing enzyme of ADMA, in cultured endothelial cells. ALA significantly decreased ADMA level in culture media of endothelial cells. ALA increased the gene expression and activity of DDAH, and signal transducer and activator of transcription (STAT)3 phosphorylation. Transfection of STAT3 increased DDAH II promoter activity, and ALA amplified it. ALA-induced increase in DDAH II promoter activity was attenuated in the promoter that had mutation in putative STAT3-binding site. These results suggest that ALA reduces ADMA level by enhancing DDAH activity and DDAH II gene expression, thus providing a novel mechanism by which ALA regulates endothelial function.
