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Immunological reconstitution

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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
#1
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
#2
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
#3
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
#4
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). Additionally, mTECs-derived factors have been implicated in the recruitment of thymic dendritic cells (DCs) and intrathymic DC development...
September 11, 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
#5
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
#6
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
#7
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
#8
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
#9
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)...
July 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28720549/evolutionary-basis-of-a-new-approach-for-the-treatment-of-malignant-brain-tumors-from-mice-to-humans
#10
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
#11
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
https://www.readbyqxmd.com/read/28699851/dynamics-of-cd4-cell-count-among-hiv-infected-individuals-in-lagos-nigeria
#12
Babatunde O Motayo, Babatunde A Olusola, Adedayo O Faneye, Solomon Aturaka, Olukunle Oluwasemowo, Joseph I Ogiogwa
Human immunodeficiency virus (HIV) infection leads to progressive loss of CD4 T cells. Antiretroviral therapy has been able to inhibit this process, resulting in significant level of immune recovery and function. Our aim is to investigate the dynamics of CD4 recovery among HIV patients in Lagos, Nigeria. A total of 213 HIV-positive individuals were enrolled between October 2007 and May 2008, and followed up for 9 months based on CD4 count. CD4 analysis was done by flow cytometry at enrollment and after every 3 months...
July 12, 2017: Journal of Immunoassay & Immunochemistry
https://www.readbyqxmd.com/read/28621766/autologous-haematopoietic-stem-cell-transplantation-for-treatment-of-multiple-sclerosis
#13
REVIEW
Paolo A Muraro, Roland Martin, Giovanni Luigi Mancardi, Richard Nicholas, Maria Pia Sormani, Riccardo Saccardi
Autologous haematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from haematopoietic stem cells. Originally developed for the treatment of haematological malignancies, the procedure has been adapted for the treatment of severe immune-mediated disorders. Results from ∼20 years of research make a compelling case for selective use of AHSCT in patients with highly active multiple sclerosis (MS), and for controlled trials...
July 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28617830/on-treatment-decrease-of-nkg2d-correlates-to-early-emergence-of-clinically-evident-hepatocellular-carcinoma-after-interferon-free-therapy-for-chronic-hepatitis-c
#14
Po-Sung Chu, Nobuhiro Nakamoto, Nobuhito Taniki, Keisuke Ojiro, Takeru Amiya, Yuko Makita, Hiroko Murata, Akihiro Yamaguchi, Shunsuke Shiba, Rei Miyake, Tadashi Katayama, Aya Ugamura, Akihiko Ikura, Karin Takeda, Hirotoshi Ebinuma, Hidetsugu Saito, Takanori Kanai
BACKGROUND AND AIMS: Interferon (IFN)- free direct antiviral agents (DAAs) with rapid HCV eradication might evoke immunological reconstitutions, and some early recurrences of HCC after IFN-free DAAs have been reported. This study aimed to investigate whether natural killer group 2, member D (NKG2D) predicts early emergence of HCC after IFN-free DAAs. METHODS: We conducted a clinical practice-based observational study of 101 patients infected with genotype 1 HCV who received IFN-free (DAAs), and stratified them into those who did or did not develop early (i...
2017: PloS One
https://www.readbyqxmd.com/read/28612841/il-17-driven-intestinal-fibrosis-is-inhibited-by-itch-mediated-ubiquitination-of-hic-5
#15
J Paul, A K Singh, M Kathania, T L Elviche, M Zeng, V Basrur, A L Theiss, K Venuprasad
Intestinal fibrosis is a major complication in inflammatory bowel diseases, but the regulatory mechanism that inhibits fibrosis remains unclear. Here we demonstrate that Itch(-/-)myofibroblasts express increased amounts of profibrotic collagen type I and α-SMA in response to IL-17. Mechanistically, we demonstrate that Itch directly binds to HIC-5 and targets it for K63-linked ubiquitination to inhibit IL-17-driven intestinal fibrosis. Reconstitution of Itch(-/-) myofibroblasts with wild-type Itch but not the Itch-C830A mutant normalized the expression of profibrotic genes...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28559819/two-year-complete-remission-of-diffuse-large-b-cell-lymphoma-in-an-immunological-nonresponder-hiv-infected-patient-case-report
#16
Miodrag Vrbic, Ivan Petkovic, Svetislav Vrbic, Maja Jovanovic, Aleksandar Rankovic, Lidija Popovic-Dragonjic, Marina Djordjevic-Spasic
INTRODUCTION: HIV-infected patients are affected significantly more frequently by all types of lymphoma, with diffuse large B-cell lymphoma (DLBCL) as the most prevalent histological type. Since the introduction of combination antiretroviral therapy (cART) morbidity and mortality of DLBCL has been markedly reduced, which is primarily interpreted as a result of the drug-mediated immune reconstitution. CASE REPORT: We present a previously healthy, 44-year-old HIV-infected man with DLBCL of the oral cavity, treated with immunochemotherapy and cART...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28552210/immune-reconstitution-inflammatory-syndrome-iris-what-pathologists-should-know
#17
REVIEW
Ann Marie Nelson, Yukari C Manabe, Sebastian B Lucas
Antiretroviral therapy has significantly improved the quality and length of life for those patients able to access effective and sustained treatment. The resulting restoration of the immune response is associated with a change in the clinical presentation of opportunistic infections, and the histologic reaction to pathogens. A complex combination of alterations in host response across the stages of HIV infection has been documented over the past 3 decades. The defects are seen in both acute and chronic phases of inflammation and involve innate and adaptive immunity...
July 2017: Seminars in Diagnostic Pathology
https://www.readbyqxmd.com/read/28542787/understanding-the-reconstitution-of-the-b-cell-compartment-in-bone-marrow-and-blood-after-treatment-for-b-cell-precursor-acute-lymphoblastic-leukaemia
#18
Prisca M J Theunissen, Anouk van den Branden, Alita Van Der Sluijs-Gelling, Valerie De Haas, Auke Beishuizen, Jacques J M van Dongen, Vincent H J Van Der Velden
A better understanding of the reconstitution of the B-cell compartment during and after treatment in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) will help to assess the immunological status and needs of post-treatment BCP-ALL patients. Using 8-colour flow cytometry and proliferation-assays, we studied the composition and proliferation of both the B-cell precursor (BCP) population in the bone marrow (BM) and mature B-cell population in peripheral blood (PB) during and after BCP-ALL therapy. We found a normal BCP differentiation pattern and a delayed formation of classical CD38(dim) -naive mature B-cells, natural effector B-cells and memory B-cells in patients after chemotherapy...
July 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28498953/pathological-role-of-anti-cd4-antibodies-in-hiv-infected-immunologic-nonresponders-receiving-virus-suppressive-antiretroviral-therapy
#19
Zhenwu Luo, Zhen Li, Lisa Martin, Zhuang Wan, Eric G Meissner, Enrique Espinosa, Hao Wu, Xiaocong Yu, Pingfu Fu, Maria Anna Julia Westerink, J Michael Kilby, Jennifer Wu, Lei Huang, Sonya L Heath, Zihai Li, Wei Jiang
Increased mortality and morbidity occur among human immunodeficiency virus (HIV)-infected patients in whom CD4+ T-cell counts do not increase despite viral suppression with antiretroviral therapy (ART). Here we identified an underlying mechanism. Significantly elevated plasma levels of anti-CD4 immunoglobulin G (IgG) were found in HIV-positive immunologic nonresponders (ie, HIV-positive individuals with CD4+ T-cell counts of ≤350 cells/μL), compared with levels in HIV-positive immunologic responders (ie, HIV-positive individuals with CD4+ T-cell counts of ≥500 cells/μL) and healthy controls...
July 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28485401/foxp3-regulatory-t-cells-maintain-the-bone-marrow-microenvironment-for-b-cell-lymphopoiesis
#20
Antonio Pierini, Hidekazu Nishikii, Jeanette Baker, Takaharu Kimura, Hye-Sook Kwon, Yuqiong Pan, Yan Chen, Maite Alvarez, William Strober, Andrea Velardi, Judith A Shizuru, Joy Y Wu, Shigeru Chiba, Robert S Negrin
Foxp3(+) regulatory T cells (Treg cells) modulate the immune system and maintain self-tolerance, but whether they affect haematopoiesis or haematopoietic stem cell (HSC)-mediated reconstitution after transplantation is unclear. Here we show that B-cell lymphopoiesis is impaired in Treg-depleted mice, yet this reduced B-cell lymphopoiesis is rescued by adoptive transfer of affected HSCs or bone marrow cells into Treg-competent recipients. B-cell reconstitution is abrogated in both syngeneic and allogeneic transplantation using Treg-depleted mice as recipients...
May 9, 2017: Nature Communications
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