scholarly journals Minor H Antigen HA-1–specific Regulator and Effector CD8+ T Cells, and HA-1 Microchimerism, in Allograft Tolerance

2004 ◽  
Vol 199 (7) ◽  
pp. 1017-1023 ◽  
Author(s):  
Junchao Cai ◽  
Junglim Lee ◽  
Ewa Jankowska-Gan ◽  
Richard Derks ◽  
Jos Pool ◽  
...  

The role of the hematopoietic lineage-restricted minor histocompatibility (H) antigen HA-1 in renal allograft tolerance was explored. We obtained peripheral blood samples from three recipients of histocompatibility leukocyte antigen (HLA)–matched, HA-1–mismatched renal transplants, one of which had discontinued immunosuppression >30 yr ago while sustaining normal kidney function. Peripheral blood mononuclear cells (PBMCs) were injected into the footpads of severe combined immunodeficiency mice to measure human delayed type hypersensitivity (DTH) responses. All three patients manifested regulated DTH responses to HA-1H peptide. By differential tetramer staining intensities, we observed two distinct minor H antigen HA-1–specific CD8+ T cell subsets. The one that stained dimly had the characteristics of a T regulatory (TR) cell and produced interleukin (IL) 10 and/or transforming growth factor (TGF) β. These HA-1–specific TR cells coexisted with bright tetramer-binding CD8+ T effector (TE) cells. The CD8+ TE cells mediated HA-1–specific DTH and produced interferon-γ. Suppression of these TE functions by TR cells was TGFβ, IL-10, and cytotoxic T lymphocyte–associated antigen 4 dependent. In addition, HA-1 microchimerism was detected in two recipients, primarily in the dendritic cell fraction of the PBMCs. This is the first demonstration of coexisting CD8+ memory TR and TE cells, both specific for the same HA-1 antigen, in the context of renal allograft tolerance.

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Reetta Holma ◽  
Riina A. Kekkonen ◽  
Katja Hatakka ◽  
Tuija Poussa ◽  
Outi Vaarala ◽  
...  

Probiotics and prebiotics modify the intestinal environment and could have immunomodulatory effects. The proliferation of spontaneous and phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs) and their production of interleukin-4, interleukin-5, transforming growth factor-β1, and interferon-γ (IFNγ) were determined in eighteen men at the baseline and during a 2-week period of probiotics (mixture of Lactobacillus rhamnosus GG, Lactobacillus rhamnosus LC705, Propionibacterium freudenreichii ssp. shermanii JS, and Bifidobacterium breve Bb99) and galactooligosaccharides (GOSs) (3.8 g/day). The spontaneous and stimulated proliferation of PBMC increased from the baseline during probiotics+GOS (P<0.001). The secretion of IFNγ, but not other cytokines, by stimulated PBMC increased during the same period (P<0.05). In conclusion, the consumption of this probiotic mixture including GOS appears to increase the capacity of PBMC to proliferate and release IFNγ selectively in healthy men.


2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Hung-Ju Lin ◽  
Sung-Liang Yu ◽  
Ta-Chen Su ◽  
Hsiu-Ching Hsu ◽  
Ming-Fong Chen ◽  
...  

Abstract Statins inhibit cholesterol biogenesis and modulate atheroma inflammation to reduce cardiovascular risks. Promoted by immune and non-immune cells, serum C-reactive protein (CRP) might be a biomarker suboptimal to assess inflammation status. Although it has been reported that statins modulated inflammation via microRNAs (miRNAs), evidence remains lacking on comprehensive profiling of statin-induced miRNAome alterations in immune cells. We recruited 19 hypercholesterolemic patients receiving 2 mg/day pitavastatin and 15 ones receiving 10 mg/day atorvastatin treatment for 12 weeks, and performed microarray-based profiling of 1733 human mature miRNAs in peripheral blood mononuclear cells (PBMCs) before and after statin treatment. Differentially expressed miRNAs were determined if their fold changes were &gt;1.50 or &lt;0.67, after validated using quantitative polymerase chain reaction (qPCR). The miRSystem and miTALOS platforms were utilized for pathway analysis. Of the 34 patients aged 63.7 ± 6.2 years, 27 were male and 19 were with coronary artery disease. We discovered that statins induced differential expressions of miR-483-5p, miR-4667-5p, miR-1244, and miR-3609, with qPCR-validated fold changes of 1.74 (95% confidence interval, 1.33–2.15), 1.61 (1.25–1.98), 1.61 (1.01–2.21), and 1.68 (1.19–2.17), respectively. The fold changes of the four miRNAs were not correlated with changes of low-density-lipoprotein cholesterol or CRP, after sex, age, and statin type were adjusted. We also revealed that RhoA and transforming growth factor-β signaling pathways might be regulated by the four miRNAs. Given our findings, miRNAs might be involved in statin-induced inflammation modulation in PBMCs, providing likelihood to assess and reduce inflammation in patients with atherosclerotic cardiovascular diseases.


2018 ◽  
Vol 51 (3) ◽  
pp. 1701124 ◽  
Author(s):  
Caroline E. Broos ◽  
Laura L. Koth ◽  
Menno van Nimwegen ◽  
Johannes C.C.M. in ‘t Veen ◽  
Sandra M.J. Paulissen ◽  
...  

The lung-draining mediastinal lymph nodes (MLNs) are currently widely used to diagnose sarcoidosis. We previously reported that T-helper (Th) 17.1 cells are responsible for the exaggerated interferon-γ production in sarcoidosis lungs. In this study, we aimed to investigate 1) whether Th17.1 cells are also increased in the MLNs of sarcoidosis patients and 2) whether frequencies of the Th17.1 cells at diagnosis may correlate with disease progression.MLN cells from treatment-naive pulmonary sarcoidosis patients (n=17) and healthy controls (n=22) and peripheral blood mononuclear cells (n=34) and bronchoalveolar lavage fluid (BALF) (n=36) from sarcoidosis patients were examined for CD4+ T-cell subset proportions using flow cytometry.Higher proportions of Th17.1 cells were detected in sarcoidosis MLNs than in control MLNs. Higher Th17.1 cell proportions were found in sarcoidosis BALF compared with MLNs and peripheral blood. Furthermore, BALF Th17.1 cell proportions were significantly higher in patients developing chronic disease than in patients undergoing resolution within 2 years of clinical follow-up.These data suggest that Th17.1 cell proportions in pulmonary sarcoidosis can be evaluated as a diagnostic and/or prognostic marker in clinical practice and could serve as a new therapeutic target.


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