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Immunological reconstitution

Ashley I Beyer, Marcus O Muench
Immunodeficient mice play a critical role in hematology research as in vivo models of hematopoiesis and immunology. Multiple strains have been developed, but hematopoietic stem cell engraftment and immune reconstitution have not been methodically compared among them. Four mouse strains were transplanted with human fetal bone marrow or adult peripheral blood CD34+ cells: NSG, NSG-3GS, hSCF-Tg-NSG and hSIRPα-DKO. Hematopoietic engraftment in the bone marrow, blood, spleen and liver was evaluated by flow cytometry 12 weeks after transplant...
October 19, 2016: Stem Cells and Development
Palash Samanta, Nina Singh
Opportunistic mycoses remain a significant complication in organ recipients. Areas covered: This review is an evidence-based presentation of current state-of-knowledge and our perspective on recent developments in the field Expert commentary: Invasive fungal infections are associated with reduced allograft and patient survival, increase in healthcare resource utilization, and newly appreciated but largely unrecognized immunologic sequelae, such as immune reconstitution syndrome. Given adverse outcomes associated with established infections, prophylaxis is a widely used strategy for the prevention of these infections...
October 3, 2016: Expert Review of Anti-infective Therapy
Valerio Rossini, Katarina Radulovic, Christian U Riedel, Jan Hendrik Niess
Inflammatory bowel disease (IBD) is a chronic inflammation which affects the gastrointestinal tract (GIT). One of the best ways to study the immunological mechanisms involved during the disease is the T cell transfer model of colitis. In this model, immunodeficient mice (RAG(-/-) recipients) are reconstituted with naive CD4(+) T cells from healthy wild type hosts. This model allows examination of the earliest immunological events leading to disease and chronic inflammation, when the gut inflammation perpetuates but does not depend on a defined antigen...
2016: Journal of Visualized Experiments: JoVE
C Y Leng, H C Low, L L Chua, M L Chong, H Sulaiman, I Azwa, J M Roberts, A Kamarulzaman, R Rajasuriar, Y L Woo
OBJECTIVES: Human papillomavirus (HPV)-associated cancers disproportionately affect those infected with HIV despite effective combination antiretroviral therapy (cART). The primary aim of this study was to quantify HPV16 and HPV52 E6-specific interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) T-cell responses, a correlate of protective immunity, in the first year following cART initiation and subsequently in those patients with suboptimal (sIR) and optimal (oIR) immune reconstitution...
September 20, 2016: HIV Medicine
Herry Mapesi, Adrià Ramírez, Marcel Tanner, Christoph Hatz, Emilio Letang
BACKGROUND: Immune reconstitution inflammatory syndrome associated with dermatophytoses (tinea-IRIS) may cause considerable morbidity. Yet, it has been scarcely reported and is rarely considered in the differential diagnosis of HIV associated cutaneous lesions in Africa. If identified, it responds well to antifungals combined with steroids. We present two cases of suspected tinea-immune reconstitution inflammatory syndrome from a large HIV clinic in rural Tanzania. CASES PRESENTATION: A first case was a 33 years-old female newly diagnosed HIV patient with CD4 count of 4 cells/μL (0 %), normal complete blood count, liver and renal function tests was started on co-formulated tenofovir/emtricitabine/efavirenz and prophylactic cotrimoxazole...
2016: BMC Infectious Diseases
Jing Deng, Yu-Ya Mitsuki, Guomiao Shen, Jocelyn Ray, Claudia Cicala, James Arthos, Michael L Dustin, Catarina E Hioe
: HIV is transmitted most efficiently from cell to cell and productive infection occurs mainly in activated CD4 T cells. It is postulated that HIV exploits immunological synapses formed between CD4 T cells and antigen-presenting cells to facilitate the targeting and infection of activated CD4 T cells. This study sought to evaluate how the presence of the HIV envelope (Env) in the CD4 T cell immunological synapse affects synapse formation and intracellular signaling to impact the downstream T cell activation events...
September 14, 2016: Journal of Virology
Joseph C Mudd, Jason M Brenchley
Distinct pathological events occur within the gastrointestinal (GI) tract of Asian macaques with progressive simian immunodeficiency virus (SIV) infection and humans with human immunodeficiency virus type 1 (HIV-1) infection that are critical in shaping disease course. These events include depletion and functional alteration of GI-resident CD4(+) T cells, loss of antigen-presenting cells, loss of innate lymphocytes, and possible alterations to the composition of the gut microbiota. These contribute to structural damage to the GI tract and systemic translocation of GI tract microbial products...
October 1, 2016: Journal of Infectious Diseases
Frédéric Vély, Vincent Barlogis, Blandine Vallentin, Bénédicte Neven, Christelle Piperoglou, Thibaut Perchet, Maxime Petit, Nadia Yessaad, Fabien Touzot, Julie Bruneau, Nizar Mahlaoui, Nicolas Zucchini, Catherine Farnarier, Gérard Michel, Despina Moshous, Stéphane Blanche, Arnaud Dujardin, Hergen Spits, Jörg H W Distler, Andreas Ramming, Capucine Picard, Rachel Golub, Alain Fischer, Eric Vivier
Innate lymphoid cells (ILCs) have potent immunological functions in experimental conditions in mice, but their contributions to immunity in natural conditions in humans have remained unclear. We investigated the presence of ILCs in a cohort of patients with severe combined immunodeficiency (SCID). All ILC subsets were absent in patients with SCID who had mutation of the gene encoding the common γ-chain cytokine receptor subunit IL-2Rγ or the gene encoding the tyrosine kinase JAK3. T cell reconstitution was observed in patients with SCID after hematopoietic stem cell transplantation (HSCT), but the patients still had considerably fewer ILCs in the absence of myeloablation than did healthy control subjects, with the exception of rare cases of reconstitution of the ILC1 subset of ILCs...
September 12, 2016: Nature Immunology
Drake J Smith, Levina J Lin, Heesung Moon, Alexander T Pham, Xi Wang, Siyuan Liu, Sunjong Ji, Valerie Rezek, Saki Shimizu, Marlene Ruiz, Jennifer Lam, Deanna M Janzen, Sanaz Memarzadeh, Donald B Kohn, Jerome A Zack, Scott G Kitchen, Dong Sung An, Lili Yang
The humanized bone marrow-liver-thymus (BLT) mouse model harbors a nearly complete human immune system, therefore providing a powerful tool to study human immunology and immunotherapy. However, its application is greatly limited by the restricted supply of human CD34(+) hematopoietic stem cells and fetal thymus tissues that are needed to generate these mice. The restriction is especially significant for the study of human immune systems with special genetic traits, such as certain human leukocyte antigen (HLA) haplotypes or monogene deficiencies...
October 18, 2016: Stem Cells and Development
Christina C Chang, John R Perfect
PURPOSE OF REVIEW: Overall, 50-70% of patients with cryptococcal meningitis have raised intracranial pressure (ICP). Multiple international treatment guidelines recommend repeated therapeutic lumbar punctures as adjunctive management. Here, we review the recent evidence for the role of repeated lumbar punctures on clinical outcome in cryptococcal meningitis and also review the increasing body of data utilizing these repeated cerebrospinal fluid (CSF) samples as a window into understanding immunopathogenesis of cryptococcal meningitis...
September 6, 2016: Current Opinion in Infectious Diseases
Kristjana H Ásbjörnsdóttir, James P Hughes, Dalton Wamalwa, Agnes Langat, Jennifer A Slyker, Hellen Moraa Okinyi, Julie Overbaugh, Sarah Benki-Nugent, Kenneth Tapia, Elizabeth Maleche-Obimbo, Ali Rowhani-Rahbar, Grace John-Stewart
BACKGROUND: Virologic and immunologic responses to antiretroviral treatment (ART) in infants may differ from older children due to immunologic, clinical or epidemiologic characteristics. METHODS: Longitudinal ART responses were modeled and compared in HIV-infected infants and children enrolled in cohorts in Nairobi, Kenya. Participants were enrolled soon after HIV diagnosis, started on ART, and followed for two years. Viral load decline was compared between infant and child cohorts using a nonlinear mixed effects model and CD4% reconstitution using a linear mixed effects model...
September 6, 2016: AIDS
Timothy L Pruett
Chemotherapeutic agents for Hepatitis B virus (HBV) suppression work, but only when administered to the patient. They do not appear to promote durable, long-term immunological control. After 3 years of effective anti-HBV therapy, a small percentage of patients maintained good control, manifest by controlled serum liver enzymes, low-level HBV-DNA, and controlled HBsAg concentrations. However, this did not occur in the majority of patients. We need a better understanding of the defects in HBV immunity and how to induce effective reconstitution that will maintain viral suppression, albeit either through innate or adaptive immunity...
September 2016: American Journal of Gastroenterology
Zachariah DeFilipp, Yi-Bin Chen
Disease relapse is a major barrier to successful allogeneic hematopoietic cell transplantation (HCT). Maintenance therapy administered after HCT is a promising strategy to attempt to reduce relapse and improve overall survival. However, many questions and challenges remain regarding this approach, including which patients should receive maintenance therapy, which agents should be used, what the ideal duration of therapy is, and what effect specific agents will have on toxicities, immunological reconstitution and graft-versus-host disease...
August 24, 2016: Biology of Blood and Marrow Transplantation
Chiara Bacchelli, Federico A Moretti, Marlene Carmo, Stuart Adams, Horia C Stanescu, Kerra Pearce, Manisha Madkaikar, Kimberly C Gilmour, Adeline K Nicholas, C Geoffrey Woods, Robert Kleta, Phil L Beales, Waseem Qasim, H Bobby Gaspar
BACKGROUND: Signaling through the T-cell receptor (TCR) is critical for T-cell development and function. Linker for activation of T cells (LAT) is a transmembrane adaptor signaling molecule that is part of the TCR complex and essential for T-cell development, as demonstrated by LAT-deficient mice, which show a complete lack of peripheral T cells. OBJECTIVE: We describe a pedigree affected by a severe combined immunodeficiency phenotype with absent T cells and normal B-cell and natural killer cell numbers...
July 15, 2016: Journal of Allergy and Clinical Immunology
Zoë R Wallace, Sharon Sanderson, Anna Katarina Simon, Lucy Dorrell
Zidovudine (ZDV) is a widely used component of antiretroviral therapy (ART) in resource-limited settings, despite its known adverse effects, which include mitochondrial toxicity in muscle, liver and adipose tissue. It has also been associated with impaired immunological recovery. We hypothesised that ZDV might impair mitochondrial health and survival of primary T cells. We performed a cross-sectional analysis of mitochondrial function, mitophagy and susceptibility to apoptosis in healthy donor primary T cells after exposure to ZDV in vitro, together with T cells from patients who were virologically suppressed on ZDV-containing ART regimens for ≥1 year and age-matched subjects receiving non-ZDV ART regimens...
September 2016: Antiviral Research
Daniele Lilleri, Giuseppe Gerna
Human cytomegalovirus (HCMV) represents the major viral complication after hematopoietic stem cell transplantation. HCMV infection may be controlled by the reconstituting immune system and remain subclinical or can lead to severe systemic and/or organ disease (mainly pneumonia and gastroenteritis) when immune reconstitution is delayed or impaired. In order to prevent the occurrence of HCMV disease, a prompt diagnosis of HCMV infection is mandatory. The adoption of pre-emptive therapy strategies guided by virological monitoring dramatically reduced the occurrence of HCMV disease...
September 2016: Immunotherapy
P W Atipo-Tsiba, E S Kombo Bayonne
BACKGROUND: In countries with high prevalence of HIV/AIDS infection, particularly in black Africa, shingles is one of the main opportunistic infections during immunosuppression due to AIDS in young patients. If immunological weakness is important, usually when the CD4 cell count is less than 100 cells/mm(3), the risk of inflammatory reactions in the first three months after initiating of antiretroviral treatment (ART) is very high. This inflammatory reaction is called immune reconstitution inflammatory syndrome (IRIS)...
May 2016: Ethiopian Journal of Health Sciences
Vahid Bayati, Mohammad Reza Abbaspour, Fereshteh Negad Dehbashi, Niloofar Neisi, Mahmoud Hashemitabar
Polycaprolactone (PCL) is used as a material of choice for surgical sutures, wound dressings, contraceptives, fixation devices and dentistry in paramedical sciences. In addition, adipose-derived stem cells (ASCs) have been shown to be effective in the treatment of acute and chronic wounds. This study aimed to evaluate the effect of electrospun PCL fibers on keratinocyte differentiation of ASCs and wound healing. PCL solution was electrospun and characterized. Isolated and characterized ASCs were differentiated into keratinocyte-like cells on a tissue culture plate (TCP) and PCL matrices and compared...
June 21, 2016: Anatomical Science International
Lucas C M Arruda, Júlia T C de Azevedo, Gislane L V de Oliveira, Gabriela T Scortegagna, Evandra S Rodrigues, Patrícia V B Palma, Doralina G Brum, Carlos T Guerreiro, Vanessa D Marques, Amilton A Barreira, Dimas T Covas, Belinda P Simões, Júlio C Voltarelli, Maria Carolina Oliveira, Kelen C R Malmegrim
High dose immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) induces prolonged clinical remission in multiple sclerosis (MS) patients. However, how patient immune profiles are associated with clinical outcomes has not yet been completely elucidated. In this study, 37 MS patients were assessed for neurological outcomes, thymic function and long-term immune reconstitution after AHSCT. Patients were followed for a mean (SD) of 68.5 (13.9) months post-transplantation and were retrospectively clustered into progression- and non-progression groups, based on Expanded Disease Status Scale (EDSS) outcomes at last visit...
August 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Martin K Thomsen, Ramya Nandakumar, Daniela Stadler, Antje Malo, Roser Marin Valls, Fan Wang, Line S Reinert, Frederik Dagnaes-Hansen, Anne Kruse Hollensen, Jacob Giehm Mikkelsen, Ulrike Protzer, Søren R Paludan
UNLABELLED: Hepatitis B virus (HBV) is a major human pathogen, and about one third of the global population will be exposed to the virus in their lifetime. HBV infects hepatocytes, where it replicates its DNA and infection can lead to acute and chronic hepatitis with a high risk of liver cirrhosis and hepatocellular carcinoma. Despite this, there is limited understanding of how HBV establishes chronic infections. In recent years it has emerged that foreign DNA potently stimulates the innate immune response, particularly type 1 interferon (IFN) production; and this occurs through a pathway dependent on the DNA sensor cyclic guanosine monophosphate-adenosine monophosphate synthase and the downstream adaptor protein stimulator of IFN genes (STING)...
September 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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