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iNKT and transplantation

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https://www.readbyqxmd.com/read/27799307/nkt-cell-deficient-mice-harbor-an-altered-microbiota-that-fuels-intestinal-inflammation-during-chemically-induced-colitis
#1
Thirumahal Selvanantham, Qiaochu Lin, Cynthia Xinyi Guo, Anuradha Surendra, Stephanie Fieve, Nichole K Escalante, David S Guttman, Catherine J Streutker, Susan J Robertson, Dana J Philpott, Thierry Mallevaey
NKT cells are unconventional T cells that respond to self and microbe-derived lipid and glycolipid Ags presented by the CD1d molecule. Invariant NKT (iNKT) cells influence immune responses in numerous diseases. Although only a few studies have examined their role during intestinal inflammation, it appears that iNKT cells protect from Th1-mediated inflammation but exacerbate Th2-mediated inflammation. Studies using iNKT cell-deficient mice and chemically induced dextran sodium sulfate (DSS) colitis have led to inconsistent results...
October 31, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27740636/pre-transplant-donor-cd4-invariant-nkt-cell-expansion-capacity-predicts-the-occurrence-of-acute-graft-versus-host-disease
#2
M-T Rubio, M Bouillié, N Bouazza, T Coman, H Trebeden-Nègre, A Gomez, F Suarez, D Sibon, A Brignier, E Paubelle, S Nguyen-Khoc, M Cavazzana, O Lantz, M Mohty, S Urien, O Hermine
Clinically useful pre-transplant predictive factors of acute graft-versus-host-disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) are lacking. We prospectively analyzed HSC graft content in CD34(+), NK, conventional T, regulatory T and invariant NKT (iNKT) cells in 117 adult patients before allo-SCT. Results were correlated with occurrence of aGVHD and relapse. In univariate analysis, iNKT cells were the only graft cell populations associated with occurrence of aGVHD. In multivariate analysis, CD4(-) iNKT/T cell frequency could predict grade II-IV aGVHD in bone marrow and peripheral blood stem cell (PBSC) grafts, while CD4(-) iNKT expansion capacity was predictive in PBSC grafts...
October 14, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27280122/generation-of-mouse-inkt-cell-lines
#3
Xiangming Li, Moriya Tsuji, Jonathan Schneck, Tonya J Webb
Natural killer T (NKT) cells bridge the innate and adaptive arms of the immune system, and manipulating their effector functions can have therapeutic significances in the treatment of autoimmunity, transplant biology, infectious disease and cancer. This important lymphocyte subset regulates the immune system through their potent cytokine production following the recognition of lipid antigen present in the context of the MHC class I-like CD1d molecule, in addition their ability to directly mediate cytotoxicity...
March 20, 2013: Bio-protocol
https://www.readbyqxmd.com/read/26903546/larger-number-of-invariant-natural-killer-t-cells-in-pbsc-allografts-correlates-with-improved-gvhd-free-and-progression-free-survival
#4
Florent Malard, Myriam Labopin, Patrice Chevallier, Thierry Guillaume, Alix Duquesne, Fanny Rialland, Sophie Derenne, Pierre Peterlin, Anne-Gaelle Leauté, Eolia Brissot, Marc Gregoire, Philippe Moreau, Philippe Saas, Béatrice Gaugler, Mohamad Mohty
We studied the impact of a set of immune cells contained within granulocyte colony-stimulating factor-mobilized peripheral blood stem cell grafts (naïve and memory T-cell subsets, B cells, regulatory T cells, invariant natural killer T cells [iNKTs], NK cells, and dendritic cell subsets) in patients (n = 80) undergoing allogeneic stem cell transplantation (SCT), using the composite end point of graft-versus-host disease (GVHD)-free and progression-free survival (GPFS) as the primary end point. We observed that GPFS incidences in patients receiving iNKT doses above and below the median were 49% vs 22%, respectively (P= ...
April 7, 2016: Blood
https://www.readbyqxmd.com/read/26878658/invariant-natural-killer-t-cells-in-hematopoietic-stem-cell-transplantation-killer-choice-for-natural-suppression
#5
REVIEW
P Guan, H Bassiri, N P Patel, K E Nichols, R Das
Invariant natural killer T cells (iNKTs) are innate-like lipid-reactive T lymphocytes that express an invariant T-cell receptor (TCR). Following engagement of the iTCR, iNKTs rapidly secrete copious amounts of Th1 and Th2 cytokines and promote the functions of several immune cells including NK, T, B and dendritic cells. Accordingly, iNKTs bridge the innate and adaptive immune responses and modulate susceptibility to autoimmunity, infection, allergy and cancer. Allogeneic hematopoietic stem cell transplantation (HSCT) is one of the most effective treatments for patients with hematologic malignancies...
May 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/26757359/nox2-activation-of-natural-killer-t-cells-is-blocked-by-the-adenosine-a2a-receptor-to-inhibit-lung-ischemia-reperfusion-injury
#6
Ashish K Sharma, Damien J LaPar, Matthew L Stone, Yunge Zhao, Christopher K Mehta, Irving L Kron, Victor E Laubach
RATIONALE: Ischemia-reperfusion (IR) injury after lung transplantation, which affects both short- and long-term allograft survival, involves activation of NADPH oxidase 2 (NOX2) and activation of invariant natural killer T (iNKT) cells to produce IL-17. Adenosine A2A receptor (A2AR) agonists are known to potently attenuate lung IR injury and IL-17 production. However, mechanisms for iNKT cell activation after IR and A2AR agonist-mediated protection remain unclear. OBJECTIVES: We tested the hypothesis that NOX2 mediates IL-17 production by iNKT cells after IR and that A2AR agonism prevents IR injury by blocking NOX2 activation in iNKT cells...
May 1, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/26495767/clonal-deletion-established-via-invariant-nkt-cell-activation-and-costimulatory-blockade-requires-in-vivo-expansion-of-regulatory-t-cells
#7
T Hirai, R Ishii, S Miyairi, M Ikemiyagi, K Omoto, Y Ishii, K Tanabe
Recently, the immune-regulating potential of invariant natural killer T (iNKT) cells has attracted considerable attention. We previously reported that a combination treatment with a liposomal ligand for iNKT cells and an anti-CD154 antibody in a sublethally irradiated murine bone marrow transplant (BMT) model resulted in the establishment of mixed hematopoietic chimerism through in vivo expansion of regulatory T cells (Tregs). Herein, we show the lack of alloreactivity of CD8(+) T cells in chimeras and an early expansion of donor-derived dendritic cells (DCs) in the recipient thymi accompanied by a sequential reduction in the donor-reactive Vβ-T cell receptor repertoire, suggesting a contribution of clonal deletion in this model...
February 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/26481260/interleukin-15-enhances-the-expansion-and-function-of-natural-killer-t-cells-from-adult-peripheral-and-umbilical-cord-blood
#8
Syh-Jae Lin, Ying-Cheng Huang, Po-Jen Cheng, Pei-Tzu Lee, Hsiu-Shan Hsiao, Ming-Ling Kuo
Invariant natural killer T cells (iNKT cells) are innate-like non-conventional T cells restricted by the CD1d molecule that are unique in their ability to play a pivotal role in immune regulation. Deficient iNKT function has been reported in patients receiving umbilical cord blood (UCB) transplantation. We sought to determine the effect of interleukin (IL)-15 on α-galactosylceramide (α-GalCer)-expanded iNKT cell function from UCB and adult peripheral blood (APB) mononuclear cells (MNCs). Fresh APB and UCB MNCs were cultured with IL-15 (50 ng/ml) in the presence or absence of α-GalCer (100 ng/ml) for 10 days...
December 2015: Cytokine
https://www.readbyqxmd.com/read/26264693/preemptive-administration-of-human-%C3%AE-%C3%AE-t-cell-receptor-targeting-monoclonal-antibody-gz-%C3%AE-%C3%AE-tcr-potently-abrogates-aggressive-graft-versus-host-disease-in-vivo
#9
Gregor Blank, Christian Welker, Bence Sipos, Katja Sonntag, Friederike Müller, Franziska Eckert, Christian Seitz, Silvio Nadalin, Gina LaCorcia, Alfred Königsrainer, Daniel Snell, Rupert Handgretinger, Karin Schilbach
GVHD, both acute and chronic, remains the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Thus, there is still a great need for therapeutic tools for the prevention and treatment of GVHD. Several biologics have shown promising results in salvage therapies but are attendant on an increased risk for opportunistic infections, lymphoproliferative disorders, and relapse. This is partly due to efficient T cell elimination that neither dissects alloreactive from non-alloreactive T cells nor considers functional and structural distinctiveness of pathogen- and malignancy-reactive γδ and iNKT T cells...
November 2015: Annals of Hematology
https://www.readbyqxmd.com/read/26232432/role-of-ship1-in-invariant-nkt-cell-development-and-functions
#10
Courtney K Anderson, Alexander I Salter, Leon E Toussaint, Emma C Reilly, Céline Fugère, Neetu Srivastava, William G Kerr, Laurent Brossay
SHIP1 is a 5'-inositol phosphatase known to negatively regulate the signaling product of the PI3K pathway, phosphatidylinositol (3-5)-trisphosphate. SHIP1 is recruited to a large number of inhibitory receptors expressed on invariant NK (iNKT) cells. We hypothesized that SHIP1 deletion would have major effects on iNKT cell development by altering the thresholds for positive and negative selection. Germline SHIP1 deletion has been shown to affect T cells as well as other immune cell populations. However, the role of SHIP1 on T cell function has been controversial, and its participation on iNKT cell development and function has not been examined...
September 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/26098781/impact-of-pre-transplant-anti-t-cell-globulin-atg-on-immune-recovery-after-myeloablative-allogeneic-peripheral-blood-stem-cell-transplantation
#11
Sophie Servais, Catherine Menten-Dedoyart, Yves Beguin, Laurence Seidel, André Gothot, Coline Daulne, Evelyne Willems, Loïc Delens, Stéphanie Humblet-Baron, Muriel Hannon, Frédéric Baron
BACKGROUND: Pre-transplant infusion of rabbit anti-T cell globulin (ATG) is increasingly used as prevention of graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (PBSCT). However, the precise impact of pre-transplant ATG on immune recovery after PBSCT is still poorly documented. METHODS: In the current study, we compared immune recovery after myeloablative PBSCT in 65 patients who either received (n = 37) or did not (n = 28) pre-transplant ATG-Fresenius (ATG-F)...
2015: PloS One
https://www.readbyqxmd.com/read/26022054/a-party-of-three-inkt-cells-in-gvhd-prevention
#12
COMMENT
Annkristin Heine, Peter Brossart
In this issue of Blood, Schneidawind et al demonstrate that the adoptive transfer of CD4+ invariant natural killer T (iNKT) cells from third-party mice protects from lethal graft-versus-host disease (GVHD) through expansion of donor regulatory T cells (Tregs) in a murine model of allogeneic hematopoietic cell transplantation (HCT).
May 28, 2015: Blood
https://www.readbyqxmd.com/read/25795920/third-party-cd4-invariant-natural-killer-t-cells-protect-from-murine-gvhd-lethality
#13
Dominik Schneidawind, Jeanette Baker, Antonio Pierini, Corina Buechele, Richard H Luong, Everett H Meyer, Robert S Negrin
Graft-versus-host disease (GVHD) is driven by extensive activation and proliferation of alloreactive donor T cells causing significant morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Invariant natural killer T (iNKT) cells are a potent immunoregulatory T-cell subset in both humans and mice. Here, we explored the role of adoptively transferred third-party CD4(+) iNKT cells for protection from lethal GVHD in a murine model of allogeneic HCT across major histocompatibility barriers...
May 28, 2015: Blood
https://www.readbyqxmd.com/read/25654212/a-locus-on-mouse-chromosome-13-inversely-regulates-cd1d-expression-and-the-development-of-invariant-natural-killer-t-cells
#14
S-W Tsaih, M Presa, S Khaja, A E Ciecko, D V Serreze, Y-G Chen
Invariant natural killer T (iNKT)-cell development is controlled by many polymorphic genes present in commonly used mouse inbred strains. Development of type 1 diabetes (T1D) in NOD mice partly results from their production of fewer iNKT-cells compared with non-autoimmune-prone control strains, including ICR. We previously identified several iNKT-cell quantitative trait genetic loci co-localized with known mouse and human T1D regions in a (NOD × ICR)F2 cross. To further dissect the mechanisms underlying the impaired iNKT-cell compartment in NOD mice, we carried out a series of bone marrow transplantation as well as additional genetic mapping studies...
April 2015: Genes and Immunity
https://www.readbyqxmd.com/read/25293774/cd4-invariant-natural-killer-t-cells-protect-from-murine-gvhd-lethality-through-expansion-of-donor-cd4-cd25-foxp3-regulatory-t-cells
#15
Dominik Schneidawind, Antonio Pierini, Maite Alvarez, Yuqiong Pan, Jeanette Baker, Corina Buechele, Richard H Luong, Everett H Meyer, Robert S Negrin
Dysregulated donor T cells lead to destruction of host tissues resulting in graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). We investigated the impact of highly purified (>95%) donor CD4(+) invariant natural killer T (iNKT) cells on GVHD in a murine model of allogeneic HCT. We found that low doses of adoptively transferred donor CD4(+) iNKT cells protect from GVHD morbidity and mortality through an expansion of donor CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs)...
November 20, 2014: Blood
https://www.readbyqxmd.com/read/25144742/innate-like-and-conventional-t-cell-populations-from-hemodialyzed-and-kidney-transplanted-patients-are-equally-compromised
#16
Marine Baron, Renata Belo, Dominique Cathelin, Lucia Moreira-Teixeira, Claire Cartery, Eric Rondeau, Laurent Mesnard, Maria Leite-de-Moraes
Clinicians are well aware of existing pharmacologically-induced immune deficient status in kidney-transplanted patients that will favor their susceptibility to bacterial or viral infections. Previous studies indicated that advanced Stage 4-5 Chronic Kidney Disease might also be regarded as an immune deficiency-like status as well, even though the mechanisms are not fully understood. Here, we analyzed the ex vivo frequency and the functional properties of both conventional and innate-like T (ILT) lymphocyte subsets in the peripheral blood of 35 patients on hemodialysis, 29 kidney transplanted patients and 38 healthy donors...
2014: PloS One
https://www.readbyqxmd.com/read/24763022/-relation-of-treg-and-inkt-cell-reconstruction-with-agvhd-after-allogeneic-hematopoietic-stem-cell-transplantation-in-children
#17
Peng-Fei Wang, Ke Huang, Jian-Pei Fang, Dun-Hua Zhou, Hai-Xia Guo, Yan-Yan Chen, Chun Chen, Yang Li
This study was aimed to explore the relation of Treg and invariant natural killer T (iNKT) cell reconstruction with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. According to the occurrence or absence of aGVHD, 29 pediatric patients who underwent allo-HSCT were firstly divided into two groups non-aGVHD and aGVHD group,then those patients with aGVHD were divided into steroid effective group and steroid resistant group according to their reaction to the steroid treatment...
April 2014: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/24586382/the-alarmin-concept-applied-to-human-renal-transplantation-evidence-for-a-differential-implication-of-hmgb1-and-il-33
#18
Antoine Thierry, Sébastien Giraud, Aurélie Robin, Anne Barra, Franck Bridoux, Virginie Ameteau, Thierry Hauet, Jean-Philippe Girard, Guy Touchard, Jean-Marc Gombert, André Herbelin
The endogenous molecules high mobility group box 1 (HMGB1) and interleukin-33 (IL-33) have been identified as alarmins, capable of mediating danger signals during tissue damage. Here, we address their possible role as innate-immune mediators in ischemia-reperfusion injury (IRI) following human kidney transplantation. We analysed serum and urinary HMGB1 and IL-33 levels, all determined by enzyme-linked immunosorbent assay, in a cohort of 26 deceased renal transplant recipients. Urinary HMGB1 and IL-33 levels were significantly increased as soon as 30 min after reperfusion, as compared to those before treatment...
2014: PloS One
https://www.readbyqxmd.com/read/24516149/mechanistic-target-of-rapamycin-complex-1-is-critical-for-invariant-natural-killer-t-cell-development-and-effector-function
#19
Jinwook Shin, Shang Wang, Wenhai Deng, Jinhong Wu, Jimin Gao, Xiao-Ping Zhong
The mechanisms that control invariant natural killer T (iNKT)-cell development and function are still poorly understood. The mechanistic or mammalian target of rapamycin (mTOR) integrates various environmental signals/cues to regulate cell growth, proliferation, metabolism, and survival. We report here that ablation of mTOR complex 1 (mTORC1) signaling by conditionally deleting Raptor causes severe defects in iNKT-cell development at early stages, leading to drastic reductions in iNKT-cell numbers in the thymus and periphery...
February 25, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/24502294/a-novel-approach-inducing-transplant-tolerance-by-activated-invariant-natural-killer-t-cells-with-costimulatory-blockade
#20
T Hirai, Y Ishii, M Ikemiyagi, E Fukuda, K Omoto, M Namiki, M Taniguchi, K Tanabe
Invariant natural killer T (iNKT) cells are one of the innate lymphocytes that regulate immunity, although it is still elusive how iNKT cells should be manipulated for transplant tolerance. Here, we describe the potential of a novel approach using a ligand for iNKT cells and suboptimal dosage of antibody for CD40-CD40 ligand (L) blockade as a powerful method for mixed chimerism establishment after allogenic bone marrow transplantation in sublethally irradiated fully allo recipients. Mixed-chimera mice accepted subsequent cardiac allografts in a donor-specific manner...
March 2014: American Journal of Transplantation
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