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Immunological reconstitution

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https://www.readbyqxmd.com/read/29163495/human-cd141-dendritic-cell-and-cd1c-dendritic-cell-undergo-concordant-early-genetic-programming-after-activation-in-humanized-mice-in-vivo
#1
Yoshihito Minoda, Isaac Virshup, Ingrid Leal Rojas, Oscar Haigh, Yide Wong, John J Miles, Christine A Wells, Kristen J Radford
Human immune cell subsets develop in immunodeficient mice following reconstitution with human CD34(+) hematopoietic stem cells. These "humanized" mice are useful models to study human immunology and human-tropic infections, autoimmunity, and cancer. However, some human immune cell subsets are unable to fully develop or acquire full functional capacity due to a lack of cross-reactivity of many growth factors and cytokines between species. Conventional dendritic cells (cDCs) in mice are categorized into cDC1, which mediate T helper (Th)1 and CD8(+) T cell responses, and cDC2, which mediate Th2 and Th17 responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29147612/low-dose-post-transplant-cyclophosphamide-can-mitigate-gvhd-and-enhance-the-g-csf-atg-induced-gvhd-protective-activity-and-improve-haploidentical-transplant-outcomes
#2
Yu Wang, Ying-Jun Chang, Lu Chen, Lan-Ping Xu, Zhi-Lei Bian, Xiao-Hui Zhang, Chen-Hua Yan, Kai-Yan Liu, Xiao-Jun Huang
Use of high-dose, post-transplant cyclophosphamide (PTCy) results in low rates of graft-versus-host-disease (GVHD) and favorable immune reconstitution, although with higher rates of relapse and somewhat high rates of graft failure. We hypothesized that permissible dose reduction of PTCy might be feasible. The current study attempts to establish a murine model and focus on regulatory T cells (Tregs) to clarify the immunological mechanisms for GVHD prevention by low-dose PTCy. In addition, a prospective, clinical cohort study in haploidentical, T-cell replete transplantation is initiated to support the rational...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29048509/plasma-but-not-cerebrospinal-fluid-interleukin-7-and-interleukin-5-levels-pre-antiretroviral-therapy-commencement-predict-cryptococcosis-associated-immune-reconstitution-inflammatory-syndrome
#3
Ngomu Akeem Akilimali, Christina C Chang, Daniel M Muema, Tarylee Reddy, Mahomed-Yunus S Moosa, Sharon R Lewin, Martyn A French, Thumbi Ndung'u
Background: Patients with human immunodeficiency virus/AIDS-associated cryptococcal meningitis (CM) frequently experience clinical deterioration, known as cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS), upon initiation of antiretroviral therapy (ART). The immunological mechanisms underlying C-IRIS are incompletely defined and no reliable predictive biomarkers exist. We investigated whether plasma or cerebrospinal fluid (CSF) levels of cytokines and chemokines predicted C-IRIS and are potential predictive biomarkers...
October 16, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29044226/bone-marrow-transplant-induced-alterations-in-notch-signaling-promote-pathologic-th17-responses-to-%C3%AE-herpesvirus-infection
#4
S J Gurczynski, X Zhou, M Flaherty, C A Wilke, B B Moore
Idiopathic pneumonia syndrome (IPS) is a common, often fatal, complication following hematopoietic stem cell transplantation (HSCT) characterized by severe pneumonitis and interstitial fibrosis. Fully reconstituted syngeneic bone marrow transplant (BMT) mice infected with murine γ-herpesvirus-68 develop interleukin-17 (IL-17)-driven pneumonitis and fibrosis, which mimics clinical manifestations of IPS. We found CD103+ and CD11b+ dendritic cells (DCs) are selectively deficient for the Notch ligand, DLL4, following BMT and CD4+ T cells isolated from lungs and spleens of infected BMT mice display Notch signaling defects...
October 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29021228/immune-reconstitution-and-survival-of-100-scid-patients-post-hematopoietic-cell-transplant-a-pidtc-natural-history-study
#5
Jennifer Heimall, Brent R Logan, Morton J Cowan, Luigi D Notarangelo, Linda M Griffith, Jennifer M Puck, Donald B Kohn, Michael A Pulsipher, Suhag Parikh, Caridad Martinez, Neena Kapoor, Richard O'Reilly, Michael Boyer, Sung-Yun Pai, Frederick Goldman, Lauri Burroughs, Sharat Chandra, Morris Kletzel, Monica Thakar, James Connelly, Geoff Cuvelier, Blachy Davila, Evan Shereck, Alan Knutsen, Kathleen E Sullivan, Kenneth DeSantes, Alfred Gillio, Elie Haddad, Aleksandra Petrovic, Troy Quigg, Angela R Smith, Elizabeth Stenger, Ziyan Yin, William T Shearer, Thomas Fleisher, Rebecca H Buckley, Christopher C Dvorak
The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treated with allogeneic hematopoietic cell transplantation (HCT) from 2010-2014, including 68 with typical SCID and 32 with leaky SCID, Omenn Syndrome or Reticular Dysgenesis. Most (59%) were diagnosed by newborn screening or family history. The 2-year overall survival (OS) was 90%but was 95% for those infection-free at HCT vs...
October 11, 2017: Blood
https://www.readbyqxmd.com/read/29020215/long-term-use-of-proton-pump-inhibitors-is-associated-with-increased-microbial-product-translocation-innate-immune-activation-and-reduced-immunologic-recovery-in-patients-with-chronic-human-immunodeficiency-virus-1-infection
#6
J A Serpa, A M Rueda, A Somasunderam, N S Utay, D Lewis, J P Couturier, K G Breaux, M Rodriguez-Barradas
Background: Translocation of microbial products from the damaged gut causes increased immune activation in human immunodeficiency virus (HIV). Proton pump inhibitors (PPIs) predispose to bacterial overgrowth in the gut. We hypothesized that long-term use of PPIs is associated with greater microbial translocation and immune activation in HIV. Methods: HIV-infected persons on suppressive antiretroviral therapy (ART), including those receiving long-term PPIs (PPI+ group) or not (PPI- group), were enrolled...
October 30, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28968425/gene-expression-profiling-of-hepatocarcinogenesis-in-a-mouse-model-of-chronic-hepatitis-b
#7
Takuto Nosaka, Tatsushi Naito, Katsushi Hiramatsu, Masahiro Ohtani, Tomoyuki Nemoto, Hiroyuki Marusawa, Ning Ma, Yusuke Hiraku, Shosuke Kawanishi, Taro Yamashita, Shuichi Kaneko, Yasunari Nakamoto
BACKGROUND: Hepatocellular carcinoma (HCC) is a common complication of chronic viral hepatitis. In support of this notion, we have reported that hepatitis B surface antigen (HBsAg)-specific CD8+ T lymphocytes critically contribute to inducing chronic liver cell injury that exerts high carcinogenic potential in a hepatitis B virus (HBV) transgenic mouse model. The dynamics of the molecular signatures responsible for hepatocellular carcinogenesis are not fully understood. The current study was designed to determine the serial changes in gene expression profiles in a model of chronic immune-mediated hepatitis...
2017: PloS One
https://www.readbyqxmd.com/read/28958808/human-innate-responses-and-adjuvant-activity-of-tlr-ligands-in-vivo-in-mice-reconstituted-with-a-human-immune-system
#8
Liang Cheng, Zheng Zhang, Guangming Li, Feng Li, Li Wang, Liguo Zhang, Sandra M Zurawski, Gerard Zurawski, Yves Levy, Lishan Su
TLR ligands (TLR-Ls) represent a class of novel vaccine adjuvants. However, their immunologic effects in humans remain poorly defined in vivo. Using a humanized mouse model with a functional human immune system, we investigated how different TLR-Ls stimulated human innate immune response in vivo and their applications as vaccine adjuvants for enhancing human cellular immune response. We found that splenocytes from humanized mice showed identical responses to various TLR-Ls as human PBMCs in vitro. To our surprise, various TLR-Ls stimulated human cytokines and chemokines differently in vivo compared to that in vitro...
October 27, 2017: Vaccine
https://www.readbyqxmd.com/read/28955330/perturbation-of-b-cell-gene-expression-persists-in-hiv-infected-children-despite-effective-antiretroviral-therapy-and-predicts-h1n1-response
#9
Nicola Cotugno, Lesley De Armas, Suresh Pallikkuth, Stefano Rinaldi, Biju Issac, Alberto Cagigi, Paolo Rossi, Paolo Palma, Savita Pahwa
Despite effective antiretroviral therapy (ART), HIV-infected individuals with apparently similar clinical and immunological characteristics can vary in responsiveness to vaccinations. However, molecular mechanisms responsible for such impairment, as well as biomarkers able to predict vaccine responsiveness in HIV-infected children, remain unknown. Following the hypothesis that a B cell qualitative impairment persists in HIV-infected children (HIV) despite effective ART and phenotypic B cell immune reconstitution, the aim of the current study was to investigate B cell gene expression of HIV compared to age-matched healthy controls (HCs) and to determine whether distinct gene expression patterns could predict the ability to respond to influenza vaccine...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28935850/viro-immunological-response-of-drug-naive-hiv-1-infected-patients-starting-a-first-line-regimen-with-viraemia-500-000-copies-ml-in-clinical-practice
#10
Maria Mercedes Santoro, Domenico Di Carlo, Daniele Armenia, Mauro Zaccarelli, Carmela Pinnetti, Manuela Colafigli, Francesca Prati, Andrea Boschi, Anna Maria Degli Antoni, Filippo Lagi, Laura Sighinolfi, Cristina Gervasoni, Massimo Andreoni, Andrea Antinori, Cristina Mussini, Carlo Federico Perno, Vanni Borghi, Gaetana Sterrantino
BACKGROUND: Virological success (VS) and immunological reconstitution (IR) of antiretroviral-naïve HIV-1 infected patients with pre-therapy viral load (VL) >500,000 copies/mL was assessed after 12 months of treatment according to initial drug-class regimens. METHODS: An observational multicenter retrospective study was performed. VS was defined as the first VL <50 copies/mL from treatment start. IR was defined as an increase of at least 150 CD4+ T-lymphocytes from treatment start...
September 22, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28931653/combined-ox40l-and-mtor-blockade-controls-effector-t-cell-activation-while-preserving-treg-reconstitution-after-transplant
#11
Victor Tkachev, Scott N Furlan, Benjamin Watkins, Daniel J Hunt, Hengqi Betty Zheng, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, John B Schell, Katie Zeleski, Alison Yu, Ian Kirby, Sarah Cooley, Jeffrey S Miller, Bruce R Blazar, Duncan Casson, Phil Bland-Ward, Leslie S Kean
A critical question facing the field of transplantation is how to control effector T cell (Teff) activation while preserving regulatory T cell (Treg) function. Standard calcineurin inhibitor-based strategies can partially control Teffs, but breakthrough activation still occurs, and these agents are antagonistic to Treg function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. In contrast, blockade of OX40L signaling has the capacity to partially control Teff activation despite maintaining Treg function...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28890868/surgical-and-immune-reconstitution-murine-models-in-bone-marrow-research-potential-for-exploring-mechanisms-in-sepsis-trauma-and-allergy
#12
REVIEW
Pedro Xavier-Elsas, Renato Nunes Ferreira, Maria Ignez C Gaspar-Elsas
Bone marrow, the vital organ which maintains lifelong hemopoiesis, currently receives considerable attention, as a source of multiple cell types which may play important roles in repair at distant sites. This emerging function, distinct from, but closely related to, bone marrow roles in innate immunity and inflammation, has been characterized through a number of strategies. However, the use of surgical models in this endeavour has hitherto been limited. Surgical strategies allow the experimenter to predetermine the site, timing, severity and invasiveness of injury; to add or remove aggravating factors (such as infection and defects in immunity) in controlled ways; and to manipulate the context of repair, including reconstitution with selected immune cell subpopulations...
August 20, 2017: World Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28890536/a-key-role-for-il-7r-in-the-generation-of-microenvironments-required-for-thymic-dendritic-cells
#13
Amanda J Moore, Tracy Sh In, Ashton Trotman-Grant, Kogulan Yoganathan, Bertrand Montpellier, Cynthia J Guidos, Juan Carlos Zúñiga-Pflücker, Michele K Anderson
Interleukin-7 receptor (IL-7R) signaling is critical for multiple stages of T-cell development, but a role in the establishment of the mature thymic architecture needed for T-cell development and thymocyte selection has not been established. Crosstalk signals between developing thymocytes and thymic epithelial cell (TEC) precursors are critical for their differentiation into cortical TECs (cTECs) and medullary TECs (mTECs). In addition, mTEC-derived factors have been implicated in the recruitment of thymic dendritic cells (DCs) and intrathymic DC development...
November 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28878127/autoantibody-producing-plasmablasts-after-b-cell-depletion-identified-in-muscle-specific-kinase-myasthenia-gravis
#14
Panos Stathopoulos, Aditya Kumar, Richard J Nowak, Kevin C O'Connor
Myasthenia gravis (MG) is a B cell-mediated autoimmune disorder of neuromuscular transmission. Pathogenic autoantibodies to muscle-specific tyrosine kinase (MuSK) can be found in patients with MG who do not have detectable antibodies to the acetylcholine receptor (AChR). MuSK MG includes immunological and clinical features that are generally distinct from AChR MG, particularly regarding responsiveness to therapy. B cell depletion has been shown to affect a decline in serum autoantibodies and to induce sustained clinical improvement in the majority of MuSK MG patients...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28826739/nk-cells-of-hiv-1-infected-patients-with-poor-cd4-t-cell-reconstitution-despite-suppressive-haart-show-reduced-ifn-%C3%AE-production-and-high-frequency-of-autoreactive-cd56-bright-cells
#15
Erica Giuliani, Lia Vassena, Silvia Di Cesare, Vincenzo Malagnino, Maria Giovanna Desimio, Massimo Andreoni, Vincenzo Barnaba, Margherita Doria
HIV-1-infected patients failing to recover CD4(+) T-cell count despite HAART (immunological non-responders, NRs), are at increased risk of disease progression and death. To better understand the NR status, we performed a comprehensive assessment of NK cells in NR patients as compared to immunologic responders. NRs exhibited an accumulation of CD56(bright) NK cells inversely correlated with CD4(+) counts. Both CD56(bright) and CD56(dim) NK cells of NRs displayed unimpaired degranulation ability, but poorly responded to cytokine stimulation in terms of NKp44 up-regulation and IFN-γ production that may explain the susceptibility of NRs to infections and tumors...
August 19, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28826735/rapid-cd4-decline-prior-to-antiretroviral-therapy-predicts-subsequent-failure-to-reconstitute-despite-hiv-viral-suppression
#16
Majid Darraj, Leigh Anne Shafer, Shanna Chan, Ken Kasper, Yoav Keynan
HIV-1 infection is characterized by loss of CD4T cells, leading to immunodeficiency. Initiation of antiretroviral therapy (ART) results in suppression of the viral load and increased CD4 counts. Both viral and host factors determine CD4 cell responses to ART with approximately 15-30% of individuals having suboptimal increase of CD4T cell count, most commonly due to lack of compliance to ART. A smaller fraction of patients will have immune reconstitution failure and suboptimal CD4 increase despite suppression of HIV replication, and these individuals are at risk for adverse health outcomes...
August 18, 2017: Journal of Infection and Public Health
https://www.readbyqxmd.com/read/28791021/reconstitution-of-t-cell-proliferation-under-arginine-limitation-activated-human-t-cells-take-up-citrulline-via-l-type-amino-acid-transporter-1-and-use-it-to-regenerate-arginine-after-induction-of-argininosuccinate-synthase-expression
#17
Anke Werner, Miriam Koschke, Nadine Leuchtner, Claudia Luckner-Minden, Alice Habermeier, Johanna Rupp, Christin Heinrich, Roland Conradi, Ellen I Closs, Markus Munder
In the tumor microenvironment, arginine is metabolized by arginase-expressing myeloid cells. This arginine depletion profoundly inhibits T cell functions and is crucially involved in tumor-induced immunosuppression. Reconstitution of adaptive immune functions in the context of arginase-mediated tumor immune escape is a promising therapeutic strategy to boost the immunological antitumor response. Arginine can be recycled in certain mammalian tissues from citrulline via argininosuccinate (ASA) in a two-step enzymatic process involving the enzymes argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28721499/treg-protected-donor-lymphocyte-infusions-a-new-tool-to-address-the-graft-versus-leukemia-effect-in-the-absence-of-graft-versus-host-disease-in-patients-relapsed-after-hsct
#18
Mauro Di Ianni, Paola Olioso, Raffaella Giancola, Stella Santarone, Annalisa Natale, Gabriele Papalinetti, Ida Villanova, Stefano Baldoni, Ambra Di Tommaso, Tiziana Bonfini, Patrizia Accorsi, Paolo Di Bartolomeo
In high-risk acute leukemia patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT), adoptive immunotherapy with T regulatory cells (Tregs) and T conventional cells (Tcons) prevented acute and chronic graft-versus-host disease (GvHD), favored post-transplant immunological reconstitution and was associated with a powerful graft-versus-leukemia (GvL) effect. With a particularly innovative approach, we developed a treatment with a Treg-protected donor lymphocyte infusion (DLI) for patients with early relapse after HSCT and we report here the results obtained in the first patient with APL (M3v) relapsed after a second matched allogeneic HSCT (15% blasts and 75% of donor cells in bone marrow)...
December 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28720549/evolutionary-basis-of-a-new-gene-and-immune-therapeutic-approach-for-the-treatment-of-malignant-brain-tumors-from-mice-to-clinical-trials-for-glioma-patients
#19
Pedro R Lowenstein, Maria G Castro
Glioma cells are one of the most aggressive and malignant tumors. Following initial surgery, and radio-chemotherapy they progress rapidly, so that patients' median survival remains under two years. They invade throughout the brain, which makes them difficult to treat, and are universally lethal. Though total resection is always attempted it is not curative. Standard of care in 2016 comprises surgical resection, radiotherapy and chemotherapy (temozolomide). Median survival is currently ~14-20months post-diagnosis though it can be higher in high complexity medical university centers, or during clinical trials...
July 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28713390/hematopoietic-stem-cell-transplantation-in-an-infant-with-immunodeficiency-centromeric-instability-and-facial-anomaly-syndrome
#20
Katharina L Gössling, Cyrill Schipp, Ute Fischer, Florian Babor, Gerhard Koch, Friedhelm R Schuster, Jutta Dietzel-Dahmen, Dagmar Wieczorek, Arndt Borkhardt, Roland Meisel, Michaela Kuhlen
Immunodeficiency, centromeric instability, and facial anomaly (ICF) syndrome is a rare autosomal recessive genetic condition with severe immunodeficiency, which leads to lethal infections if not recognized and treated in early childhood. Up-to-date treatment regimens consist of prophylactic and supportive treatment of the recurrent infections. Here, we report the case of a 1-year-old boy of Moroccan consanguineous parents, who was diagnosed at 4 months of age with ICF syndrome with a homozygous missense mutation in the DNMT3B gene...
2017: Frontiers in Immunology
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