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https://www.readbyqxmd.com/read/28802588/t-cell-costimulation-blockade-promotes-transplantation-tolerance-in-combination-with-sirolimus-and-post-transplantation-cyclophosphamide-for-haploidentical-transplantation-in-children-with-severe-aplastic-anemia
#1
Sarita Rani Jaiswal, Prakash Bhakuni, Shamsuz Zaman, Satish Bansal, Priyanka Bharadwaj, Sneh Bhargava, Suparno Chakrabarti
We conducted a pilot study employing extended T cell costimulation blockade (COSBL) with Abatacept along with sirolimus and post-transplantation cyclophosphamide (PTCy) in 10 patients (median age 12) with severe aplastic anemia (SAA). Nine patients engrafted in the COSBL group, compared to all 10 patients (median 14 vs 13days) treated on PTCy protocols without abatacept (CONTROL group). The incidence of acute graft-versus-host disease (GVHD) was 10.5% in the COSBL group compared to 50% in the CONTROL group (p=0...
August 9, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28801292/-oxidized-low-density-lipoprotein-modulates-differentiation-of-murine-memory-cd8-t-cell-subpopulations
#2
Hua Zheng, Ze-Hang Lin, Yan-Mei Zhang, Chen-Fei Zhou, Xuan Liu, Sha Wu
OBJECTIVE: To investigate effect of oxidized low-density lipoprotein (ox-LDL) on memory CD8(+) T cell subpopulation differentiation in mice with autoimmune diabetes. METHODS: Cultured splenic CD8(+) T cells from pre-diabetic NOD mice isolated with magnetic beads were treated with 30 µg/mL ox-LDL and 10 U/mL interleukin-2 (IL-2) for 24 h and the control cells were treated with IL-2 only. Flow cytometry was used to determine the percentage of splenic CD8(+)IFN-γ(+) T cells, expressions of CD8, CD44 and CD62L on the T cells, and the activation of T cell factor-1 (TCF-1) and STAT-3...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28759799/quantitative-and-qualitative-analysis-of-regulatory-t-cells-in-b-cell-chronic-lymphocytic-leukemia
#3
Vassiliki E Mpakou, Heleni-Dikaia Ioannidou, Eugene Konsta, Myrofora Vikentiou, Aris Spathis, Frieda Kontsioti, Christos K Kontos, Athanassios D Velentzas, Sotiris Papageorgiou, Diamantina Vasilatou, Konstantinos Gkontopoulos, Irene Glezou, Georgia Stavroulaki, Efthimia Mpazani, Stella Kokkori, Elias Kyriakou, Petros Karakitsos, George Dimitriadis, Vasiliki Pappa
Accumulated data indicate a significant role of T cell dysfunction in the pathogenesis of chronic lymphocytic leukemia. In CLL, regulatory T cells are significantly higher and show lower apoptotic levels compared to healthy donors. We demonstrate that CLL derived CD4(+)CD25(-)CD127(-) and CD4(+)CD25(low)CD127(-) subpopulations share a common immunophenotypic profile with conventional Tregs and are associated with advanced stage disease. We further provide evidence that the increased number of Tregs contributes indirectly to the proliferation of the CLL clone, by suppressing the proliferation of Teffs which in turn suppress CLL cells...
July 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28757397/low-utility-of-serum-25-hydroxyvitamin-d3-and-1-25-dihydroxyvitamin-d3-in-predicting-peripheral-treg-and-th17-cell-counts-in-esrd-and-renal-transplant-patients
#4
Mostafa G Aly, Li Zhu, Rolf Weimer, Gerhard Opelz, Christian Morath, Ruben Kuon, Mohammed Tohamy, Gamal Saadi, Mona Soliman, Walaa Ibrahim, Volker Daniel
BACKGROUND: Vitamin D has shown an immune-modulatory effect in different studies. Vitamin D stimulates Tregs and inhibits Th17 cells. The immune-modulatory role of vitamin D in chronic kidney disease (CKD) and renal transplant patients is unclear. We measured whether different serum levels of vitamin D were associated with an increased or decreased presence of lymphocyte subsets including Treg and Th17 cells in end-stage renal disease (ESRD) and renal transplant recipients. METHODS: Eighty-seven renal transplant recipients and 53 end-stage renal disease (ESRD) patients were enrolled in this study...
July 27, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28747257/cells-with-treg-specific-foxp3-demethylation-but-low-cd25-are-prevalent-in-autoimmunity
#5
Ricardo C Ferreira, Henry Z Simons, Whitney S Thompson, Daniel B Rainbow, Xin Yang, Antony J Cutler, Joao Oliveira, Xaquin Castro Dopico, Deborah J Smyth, Natalia Savinykh, Meghavi Mashar, Tim J Vyse, David B Dunger, Helen Baxendale, Anita Chandra, Chris Wallace, John A Todd, Linda S Wicker, Marcin L Pekalski
Identification of alterations in the cellular composition of the human immune system is key to understanding the autoimmune process. Recently, a subset of FOXP3(+) cells with low CD25 expression was found to be increased in peripheral blood from systemic lupus erythematosus (SLE) patients, although its functional significance remains controversial. Here we find in comparisons with healthy donors that the frequency of FOXP3(+) cells within CD127(low)CD25(low) CD4(+) T cells (here defined as CD25(low)FOXP3(+) T cells) is increased in patients affected by autoimmune disease of varying severity, from combined immunodeficiency with active autoimmunity, SLE to type 1 diabetes...
July 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28746881/mass-cytometric-analysis-of-hiv-entry-replication-and-remodeling-in-tissue-cd4-t-cells
#6
Marielle Cavrois, Trambak Banerjee, Gourab Mukherjee, Nandhini Raman, Rajaa Hussien, Brandon Aguilar Rodriguez, Joshua Vasquez, Matthew H Spitzer, Nicole H Lazarus, Jennifer J Jones, Christina Ochsenbauer, Joseph M McCune, Eugene C Butcher, Ann M Arvin, Nandini Sen, Warner C Greene, Nadia R Roan
To characterize susceptibility to HIV infection, we phenotyped infected tonsillar T cells by single-cell mass cytometry and created comprehensive maps to identify which subsets of CD4+ T cells support HIV fusion and productive infection. By comparing HIV-fused and HIV-infected cells through dimensionality reduction, clustering, and statistical approaches to account for viral perturbations, we identified a subset of memory CD4+ T cells that support HIV entry but not viral gene expression. These cells express high levels of CD127, the IL-7 receptor, and are believed to be long-lived lymphocytes...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28732046/qualitative-differences-in-cellular-immunogenicity-elicited-by-hepatitis-c-virus-t-cell-vaccines-employing-prime-boost-regimens
#7
Wendy G Tan, Iryna Zubkova, Alla Kachko, Frances Wells, Heiko Adler, Gerd Sutter, Marian E Major
T-cell based vaccines have been considered as attractive candidates for prevention of hepatitis C virus (HCV) infections. In this study we compared the magnitude and phenotypic characteristics of CD8+ T-cells induced by three commonly used viral vectors, Adenovirus-5 (Ad5), Vaccinia virus (VV) and Modified Vaccinia Ankara (MVA) expressing the HCV NS3/4A protein. C57/BL6 mice were primed with DNA expressing NS3/4A and boosted with each of the viral vectors in individual groups of mice. We then tracked the vaccine-induced CD8+ T-cell responses using pentamer binding and cytokine production analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28729148/clinical-grade-expanded-regulatory-t-cells-prevent-graft-versus-host-disease-while-allowing-a-powerful-t-cell-dependent-graft-versus-leukemia-effect-in-murine-models
#8
Beatrice Del Papa, Loredana Ruggeri, Elena Urbani, Stefano Baldoni, Debora Cecchini, Tiziana Zei, Roberta Iacucci Ostini, Barbara Crescenzi, Alessandra Carotti, Antonio Pierini, Paolo Sportoletti, Paolo Di Bartolomeo, Franca Falzetti, Cristina Mecucci, Andrea Velardi, Massimo F Martelli, Mauro Di Ianni
We developed a good manufacturing practices-compatible expansion protocol to improve number and purity of regulatory T cells (Tregs) available for clinical trials. Six clinical-grade separation procedures were performed, followed by expansion with high-dose interleukin (IL)-2, anti-CD3/anti-CD28 TCR stimulation, and rapamycin for 19 days achieving a median of 8.5-fold (range, 6.25 to 13.7) expansion. FOXP3 expression was stably maintained over the culture period, while the percentage of CD127 was significantly reduced...
July 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28720146/analysis-of-long-term-cd4-cd25highcd127-t-reg-cells-kinetics-in-peripheral-blood-of-lung-transplant-recipients
#9
Davide Piloni, Monica Morosini, Sara Magni, Alice Balderacchi, Luigia Scudeller, Emanuela Cova, Tiberio Oggionni, Giulia Stella, Carmine Tinelli, Filippo Antonacci, Andrea Maria D'Armini, Federica Meloni
BACKGROUND: The role of CD4(+)CD25(high)CD127(-) T-reg cells in solid-organ Transplant (Tx) acceptance has been extensively studied. In previous studies on kidney and liver recipients, peripheral T-reg cell counts were associated to graft survival, while in lung Tx, there is limited evidence for similar findings. This study aims to analyze long term peripheral kinetics of T-reg-cells in a cohort of lung recipients and tests its association to several clinical variables. METHODS: From jan 2009 to dec 2014, 137 lung Tx recipients were submitted to an immunological follow up (median: 105...
July 18, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28714519/circulating-regulatory-t-cell-subsets-predict-overall-survival-of-patients-with-unresectable-pancreatic-cancer
#10
Chen Liu, He Cheng, Guopei Luo, Yu Lu, Kaizhou Jin, Meng Guo, Quanxing Ni, Xianjun Yu
Most patients with pancreatic ductal adenocarcinoma (PDAC) have unresectable cancers with a dismal prognosis, in which cohort chemotherapy is the primary treatment. T cell immune adaption is critical for tumor immune escape and prognosis of this disease. The present study aimed to determine the correlation between peripheral T cell subset distribution in patients with unresectable PDAC and their response to chemotherapy. Two hundred and twelve patients with unresectable PDAC were included whose blood samples were collected for analysis of T cell subsets, including CD3+, CD4+, CD8+, CD8+CD28+ and CD4+CD25+CD127 T cells by flow cytometry before and after gemcitabine-based chemotherapy...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28686201/feeding-a-mixture-of-choline-forms-during-lactation-improves-offspring-growth-and-maternal-lymphocyte-response-to-ex-vivo-immune-challenges
#11
Erin D Lewis, Caroline Richard, Susan Goruk, Emily Wadge, Jonathan M Curtis, René L Jacobs, Catherine J Field
Study objectives were to examine the impact of feeding a mixture of choline forms, or a diet high in glycerophosphocholine (GPC) on maternal immune function and offspring growth during lactation. Lactating Sprague-Dawley rat dams (n = 6/diet) were randomized to one of three diets, providing 1 g/kg total choline: Control (100% free choline (FC)), Mixed Choline (MC; 50% phosphatidylcholine (PC), 25% FC, 25% GPC), or High GPC (HGPC; 75% GPC, 12.5% PC, 12.5% FC). At 3 weeks, cell phenotypes and cytokine production with Concanavalin A (ConA)-or lipopolysaccharide (LPS)-stimulated splenocytes and mesenteric lymphocytes were measured...
July 7, 2017: Nutrients
https://www.readbyqxmd.com/read/28683106/cytomegalovirus-infection-in-hiv-infected-and-uninfected-individuals-is-characterized-by-circulating-regulatory-t-cells-of-unconstrained-antigenic-specificity
#12
Adriana Tovar-Salazar, Adriana Weinberg
Cytomegalovirus (CMV) infection is associated with immune-suppression in immune-compromised hosts and old adults. We previously showed that ex vivo CMV restimulation of peripheral blood mononuclear cells (PBMC) of CMV-seropositive volunteers expanded CD4+CD27-CD28- regulatory T cells (Tregs). Here we evaluate the phenotype and function of circulating CD4+CD27-CD28- T cells of CMV-seropositive adults. Compared with CMV-seronegative, CMV-seropositive adults had 10-fold higher CD4+CD27-CD28-% T cells in PBMC. Circulating CD4+CD27-CD28- T cells from both CMV-seropositive and seronegative donors expressed higher levels of TGFβ, granzyme B, CD39, CD147 and IL-35, and lower levels of CD127, compared with their parent circulating CD4+ T cells...
2017: PloS One
https://www.readbyqxmd.com/read/28677759/analysis-of-murine-and-human-treg-subsets-in-inflammatory-bowel-disease
#13
Xiaoyun Sun, Shaoheng He, Changlong Lv, Xun Sun, Junling Wang, Wenjiao Zheng, Danan Wang
Previous studies have indicated that regulatory T cells serve essential roles in maintaining intestinal homeostasis, however, the role of different Treg subsets in modulating inflammatory bowel disease has still not been addressed clearly. In the present study, the authors measured the percentage of Foxp3+ IL‑10+ TGF‑β+ natural Tregs, Foxp3‑ IL‑10+ TGF‑β‑ induced Tregs, CD127‑ induced Tregs and CD8+ Tregs at different time points in DSS‑induced experimental colitis model in murine lamina propria lymphocytes, mesenteric lymph node and peripheral blood...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28646302/t-regulatory-cells-exhibit-a-biphasic-response-to-prolonged-endurance-exercise-in-humans
#14
Tom Clifford, Matthew J Wood, Philip Stocks, Glyn Howatson, Emma J Stevenson, Catharien M U Hilkens
PURPOSE: T-regulatory cells (Tregs) are a sub-population of lymphocytes that act to suppress aberrant immune responses. We investigated changes in the numbers of naïve and terminally differentiated Tregs in the peripheral blood to establish their role in the immuno-suppressive response to prolonged exercise. METHODS: Blood was drawn from seventeen experienced runners (age 40 ± 12 years; height 1.75 ± 0.08 m; mass 71.4 ± 10.8 kg) before, ~1 h after (POST-1h), and on the day following the marathon (POST-1d)...
August 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28645775/altered-populations-of-natural-killer-cells-cytotoxic-t-lymphocytes-and-regulatory-t-cells-in-major-depressive-disorder-association-with-sleep-disturbance
#15
Hideo Suzuki, Jonathan Savitz, T Kent Teague, Siva K Gandhapudi, Chibing Tan, Masaya Misaki, Brett A McKinney, Michael R Irwin, Wayne C Drevets, Jerzy Bodurka
A subset of individuals with major depressive disorder (MDD) have impaired adaptive immunity characterized by a greater vulnerability to viral infection and a deficient response to vaccination along with a decrease in the number and/or activity of T cells and natural killer cells (NKC). Nevertheless, it remains unclear which specific subsets of lymphocytes are altered in MDD, a shortcoming we address here by utilizing an advanced fluorescence-activated cell sorting (FACS) method that allows for the differentiation of important functionally-distinct lymphocyte sub-populations...
June 20, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28644966/an-immunosuppressive-function-of-interleukin-35-in-chronic-hepatitis-c-virus-infection
#16
Siqi Liu, Qian Zhang, Xue Shao, Wenrui Wang, Chuanhui Zhang, Zhenjing Jin
Interleukin (IL)-35, a newly identified member of the IL-12 cytokine family, has been reported to suppress inflammation and induce immunotolerance. However, little is known regarding the role of IL-35 during chronic hepatitis C virus (HCV) infection. Herein, we measured the serum IL-35 concentration of 73 patients with hepatitis C and 22 healthy individuals, as well as further investigated the modulatory function of IL-35 on CD4(+)CD25(+)CD127(dim/-) regulatory T cells (Tregs) and on hepatocytes infected with HCV in cell culture (HCVcc)...
June 20, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28638110/a-novel-and-effective-method-to-generate-human-porcine-specific-regulatory-t-cells-with-high-expression-of-il-10-tgf-%C3%AE-1-and-il-35
#17
Mingqian Li, Judith Eckl, Christiane Geiger, Dolores J Schendel, Heike Pohla
Organ transplantation remains the most effective treatment for patients with late stage organ failure. Transgenic pigs provide an alternative organ donor source to the limited availability of human organs. However, cellular rejection still remains to be the obstacle for xenotransplantation. Superior to other methods, antigen-specific regulatory T cells (Treg) alleviate cellular rejection with fewer side effects. Here we demonstrate the use of a fast method to provide tolerogenic dendritic cells (tolDC) that can be used to generate effective porcine-specific Treg cells (PSTreg)...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28620241/tgf-beta-atra-induced-tregs-express-a-selected-set-of-micrornas-involved-in-the-repression-of-transcripts-related-to-th17-differentiation
#18
Josiane Lilian Dos Santos Schiavinato, Rodrigo Haddad, Felipe Saldanha-Araujo, João Baiochi, Amélia Goes Araujo, Priscila Santos Scheucher, Dimas Tadeu Covas, Marco Antonio Zago, Rodrigo Alexandre Panepucci
Regulatory T cells (Tregs) are essential regulators of immune tolerance. atRA and TGF-β can inhibit the polarization of naïve T cells into inflammatory Th17 cells, favoring the generation of stable iTregs, however the regulatory mechanisms involved are not fully understood. In this context, the roles of individual microRNAs in Tregs are largely unexplored. Naïve T cells were immunomagnetically isolated from umbilical cord blood and activated with anti-human CD2/CD3/CD28 beads in the presence of IL-2 alone (CD4Med) or with the addition of TGF-β and atRA (CD4TGF/atRA)...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28618983/regulatory-t-cells-show-dynamic-behavior-during-late-pregnancy-delivery-and-the-postpartum-period
#19
Jorge Lima, Catarina Martins, Glória Nunes, Maria-José Sousa, Jorge C Branco, Luís-Miguel Borrego
Regulatory T cells (Tregs) are critical immunomodulators during early pregnancy by preventing maternal T-cell activation against fetal cells. However, how populations of maternal Tregs vary during and after pregnancy in humans is still unclear. Therefore, we investigated Treg subsets in the peripheral blood of pregnant women from late pregnancy through the postpartum period. To accomplish this, the following circulating Treg subsets were analyzed in 43 healthy pregnant women and 35 nonpregnant women by flow cytometry during the third trimester, on the day of delivery, and postpartum: CD4(Dim)CD25(Hi), CD4(+)CD25(Hi)Foxp3(+), and CD4(+)CD25(Hi)CD127(-/dim)...
July 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28615725/transcriptome-analysis-reveals-similarities-between-human-blood-cd3-cd56-bright-cells-and-mouse-cd127-innate-lymphoid-cells
#20
David S J Allan, Ana Sofia Cerdeira, Anuisa Ranjan, Christina L Kirkham, Oscar A Aguilar, Miho Tanaka, Richard W Childs, Cynthia E Dunbar, Jack L Strominger, Hernan D Kopcow, James R Carlyle
For many years, human peripheral blood natural killer (NK) cells have been divided into functionally distinct CD3(-) CD56(bright) CD16(-) and CD3(-) CD56(dim) CD16(+) subsets. Recently, several groups of innate lymphoid cells (ILC), distinct from NK cells in development and function, have been defined in mouse. A signature of genes present in mouse ILC except NK cells, defined by Immunological Genome Project studies, is significantly over-represented in human CD56(bright) cells, by gene set enrichment analysis...
June 14, 2017: Scientific Reports
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