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https://www.readbyqxmd.com/read/30116750/cd4-hi-cd8-low-double-positive-t-cells-are-associated-with-graft-rejection-in-a-nonhuman-primate-model-of-islet-transplantation
#1
Yun Jung Choi, Hi-Jung Park, Hye Jin Park, Kyeong Cheon Jung, Jae-Il Lee
Peripheral CD4/CD8 double-positive (DP) T cells are associated with autoimmune disorders, cancer, and viral infection. However, the relationship between organ transplantation and DP T cells is unclear. Here, we examined the functional characteristics of peripheral DP T cells and analyzed their significance with respect to islet graft rejection in a nonhuman primate model of islet transplantation. DP T cells were functionally equivalent to conventional CD4 and CD8 T cells in terms of helper and cytotoxic activity, respectively...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/30115992/il-17-dependent-siga-mediated-protection-against-nasal-bordetella-pertussis-infection-by-live-attenuated-bpze1-vaccine
#2
Luis Solans, Anne-Sophie Debrie, Lisa Borkner, Nacho Aguiló, Anaïs Thiriard, Loic Coutte, Santi Uranga, François Trottein, Carlos Martín, Kingston H G Mills, Camille Locht
BPZE1 is a live attenuated Bordetella pertussis vaccine for nasal administration to mimic the natural route of infection. Here, we studied the mechanism of BPZE1-induced immunity in the murine nasal cavity in contrast to acellular vaccine (aPV), although both vaccines protected against lung colonization. Transfer of splenocytes or serum from BPZE1-vaccinated or aPV-vaccinated mice protected naïve mice against lung colonization but not against nasal colonization. However, transfer of nasal washes from BPZE1-vaccinated mice resulted in protection against nasal colonization, which was lost in IgA-deficient or poly-Ig receptor-deficient mice, indicating that it depends on secretory IgA (SIgA) induction induced in the nose...
August 16, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/30113996/addition-of-anti-cd40-monoclonal-antibody-to-nonmyeloablative-conditioning-with-belatacept-abrogated-allograft-tolerance-despite-induction-of-mixed-chimerism
#3
Tetsu Oura, Kiyohiko Hotta, Ivy Rosales, Abbas Dehnadi, Kent Kawai, Hang Lee, A Benedict Cosimi, Tatsuo Kawai
BACKGROUND: We recently reported anti-CD40 monoclonal antibody and rapamycin (aCD40/rapa) to be a reliable, nontoxic, immunosuppressive regimen for combined islet and kidney transplantation (CIKTx) in nonhuman primates (NHPs). In the current study, we attempted to induce allograft tolerance through the mixed chimerism approach using a conditioning regimen with aCD40 and belatacept (Bela). METHODS: Five CIKTx or kidney transplant (KTx) recipients were treated with aCD40/rapa for 4 months...
August 15, 2018: Transplantation
https://www.readbyqxmd.com/read/30111631/il-21-selectively-protects-cd62l-nkt-cells-and-enhances-their-effector-functions-for-adoptive-immunotherapy
#4
Ho Ngai, Gengwen Tian, Amy N Courtney, Soodeh B Ravari, Linjie Guo, Bin Liu, Jingling Jin, Elise T Shen, Erica J Di Pierro, Leonid S Metelitsa
T cells expressing CD19-specific chimeric Ag receptors (CARs) produce high remission rates in B cell lymphoma, but frequent disease recurrence and challenges in generating sufficient numbers of autologous CAR T cells necessitate the development of alternative therapeutic effectors. Vα24-invariant NKTs have intrinsic antitumor properties and are not alloreactive, allowing for off-the-shelf use of CAR-NKTs from healthy donors. We recently reported that CD62L+ NKTs persist longer and have more potent antilymphoma activity than CD62L- cells...
August 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30110089/hypericum-perforatum-chronic-treatment-affects-cognitive-parameters-and-brain-neurotrophic-factor-levels
#5
Samira S Valvassori, Cenita Borges, Daniela V Bavaresco, Roger B Varela, Wilson R Resende, Bruna R Peterle, Camila O Arent, Josiane Budni, João Quevedo
OBJECTIVE: To evaluate the effects of Hypericum perforatum (hypericum) on cognitive behavior and neurotrophic factor levels in the brain of male and female rats. METHODS: Male and female Wistar rats were treated with hypericum or water during 28 days by gavage. The animals were then subjected to the open-field test, novel object recognition and step-down inhibitory avoidance test. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-line derived neurotrophic factor (GDNF) levels were evaluated in the hippocampus and frontal cortex...
August 9, 2018: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/30108004/cognitive-and-adaptive-outcomes-after-proton-radiation-for-pediatric-patients-with-brain-tumors
#6
Margaret B Pulsifer, Haley Duncanson, Julie Grieco, Casey Evans, Irene Delgado Tseretopoulos, Shannon MacDonald, Nancy J Tarbell, Torunn I Yock
PURPOSE: Radiation therapy is integral in treatment of pediatric brain tumors, but it is associated with negative long-term sequelae. Proton beam radiation therapy (PRT), which enables better focusing of radiation on tumors, may entail fewer sequelae. This prospective study examined cognitive and adaptive functioning in children and young adults treated with PRT. METHODS AND MATERIALS: A total of 155 patients were assessed using age-appropriate measures for cognitive and adaptive functioning at start of or during PRT (baseline) and at follow-up...
June 6, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/30107096/multiplexed-fluorescence-microscopy-reveals-heterogeneity-among-stromal-cells-in-mouse-bone-marrow-sections
#7
Karolin Holzwarth, Ralf Köhler, Lars Philipsen, Koji Tokoyoda, Valeriia Ladyhina, Carolina Wählby, Raluca A Niesner, Anja E Hauser
The bone marrow (BM) consists of multiple, structured micro-environmental entities-the so called niches, which contain hematopoietic cells as well as stromal cells. These niches fulfill a variety of functions, such as control of the hematopoietic stem cell pool, differentiation of hematopoietic cells, and maintenance of immunological memory. However, due to the molecular and cellular complexity and a lack of suitable histological multiplexing methods, the composition of the various BM niches is still elusive...
August 14, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/30105030/azithromycin-clears-bordetella-pertussis-infection-in-mice-but-also-modulates-innate-and-adaptive-immune-responses-and-t-cell-memory
#8
Lisa Borkner, Alicja Misiak, Mieszko M Wilk, Kingston H G Mills
Treatment with the macrolide antibiotic azithromycin (AZM) is an important intervention for controlling infection of children with Bordetella pertussis and as a prophylaxis for preventing transmission to family members. However, antibiotics are known to have immunomodulatory effects independent of their antimicrobial activity. Here, we used a mouse model to examine the effects of AZM treatment on clearance of B. pertussis and induction of innate and adaptive immunity. We found that treatment of mice with AZM either 7 or 14 days post challenge effectively cleared the bacteria from the lungs...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30104633/igg3-regulates-tissue-like-memory-b-cells-in-hiv-infected-individuals
#9
Lela Kardava, Haewon Sohn, Christine Youn, James W Austin, Wei Wang, Clarisa M Buckner, J Shawn Justement, Valerie A Melson, Gwynne E Roth, Marissa A Hand, Kathleen R Gittens, Richard W Kwan, Michael C Sneller, Yuxing Li, Tae-Wook Chun, Peter D Sun, Susan K Pierce, Susan Moir
Immunoglobulin G3 (IgG3) has an uncertain role in the response to infection with and vaccination against human immunodeficiency virus (HIV). Here we describe a regulatory role for IgG3 in dampening the immune system-activating effects of chronic HIV viremia on B cells. Secreted IgG3 was bound to IgM-expressing B cells in vivo in HIV-infected chronically viremic individuals but not in early-viremic or aviremic individuals. Tissue-like memory (TLM) B cells, a population expanded by persistent HIV viremia, bound large amounts of IgG3...
August 13, 2018: Nature Immunology
https://www.readbyqxmd.com/read/30104248/extending-remission-and-reversing-new-onset-type-1-diabetes-by-targeted-ablation-of-autoreactive-t-cells
#10
Kaitlin R Carroll, Eileen E Elfers, Joseph J Stevens, Jonathan P McNally, David A Hildeman, Michael B Jordan, Jonathan D Katz
Preserving endogenous insulin production is clinically advantageous and remains a vital unmet challenge in the treatment and reversal of type 1 diabetes. While broad immunosuppression has had limited success in prolonging the so-called remission period, it comes at the cost of compromising beneficial immunity. Here, we employed a novel strategy to specifically deplete the activated diabetogenic T cells that drive pathogenesis while preserving not only endogenous insulin production but also protective immunity...
August 13, 2018: Diabetes
https://www.readbyqxmd.com/read/30104244/impaired-development-and-expansion-of-germinal-center-follicular-th-cells-in-simian-immunodeficiency-virus-infected-neonatal-macaques
#11
Huanbin Xu, Widade Ziani, Jiasheng Shao, Lara A Doyle-Meyers, Kasi E Russell-Lodrigue, Marion S Ratterree, Ronald S Veazey, Xiaolei Wang
Germinal center (GC) CD4+ follicular Th (Tfh) cells are critical for cognate B cell help in humoral immune responses to pathogenic infections. Although Tfh cells are expanded or depleted in HIV/SIV-infected adults, the effects of pediatric HIV/SIV infection on Tfh cells remain unclear. In this study, we examined changes in lymphoid follicle formation in lymph nodes focusing on GC Tfh cells, B cell development, and differentiation in SIV-infected neonatal rhesus macaques ( Macaca mulatta ) compared with age-matched cohorts...
August 13, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30104107/circulating-follicular-helper-t-cells-exhibit-reduced-icos-expression-and-impaired-function-in-narcolepsy-type-1-patients
#12
Xuan-Hung Nguyen, Yves Dauvilliers, Clémence Quériault, Corine Perals, Raphaelle Romieu-Mourez, Pierre-Emmanuel Paulet, Raphaël Bernard-Valnet, Nicolas Fazilleau, Roland Liblau
Despite genetic and epidemiological evidence strongly supporting an autoimmune basis for narcolepsy type 1, the mechanisms involved have remained largely unknown. Here, we aimed to investigate whether the frequency and function of circulating follicular helper and follicular regulatory T cells are altered in narcolepsy type 1. Peripheral blood mononuclear cells were collected from 32 patients with narcolepsy type 1, including 11 who developed disease after Pandemrix® vaccination, and 32 age-, sex-, and HLA-DQB1*06:02-matched healthy individuals...
August 6, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/30103457/early-investigations-and-recent-advances-in-intraperitoneal-immunotherapy-for-peritoneal-metastasis
#13
REVIEW
Anusha Thadi, Marian Khalili, William F Morano, Scott D Richard, Steven C Katz, Wilbur B Bowne
Peritoneal metastasis (PM) is an advanced stage malignancy largely refractory to modern therapy. Intraperitoneal (IP) immunotherapy offers a novel approach for the control of regional disease of the peritoneal cavity by breaking immune tolerance. These strategies include heightening T-cell response and vaccine induction of anti-cancer memory against tumor-associated antigens. Early investigations with chimeric antigen receptor T cells (CAR-T cells), vaccine-based therapies, dendritic cells (DCs) in combination with pro-inflammatory cytokines and natural killer cells (NKs), adoptive cell transfer, and immune checkpoint inhibitors represent significant advances in the treatment of PM...
August 10, 2018: Vaccines
https://www.readbyqxmd.com/read/30103323/early-impairments-of-hippocampal-neurogenesis-in-5xfad-mouse-model-of-alzheimer-s-disease-are-associated-with-altered-expression-of-soxb-transcription-factors
#14
Ivan Zaletel, Marija Schwirtlich, Milka Perović, Mirna Jovanović, Milena Stevanović, Selma Kanazir, Nela Puškaš
 Dysregulation of neurogenesis in the subgranular zone (SGZ) of the hippocampal dentate gyrus has been related to cognitive deficits and memory loss in neurodegenerative diseases, such as Alzheimer's disease (AD). Members of the B group of SOX transcription factors play critical roles in regulating neurogenesis in the embryonic and adult nervous system, including maintaining the multipotency, renewal, and cell fate decision of neural stem/progenitor cells. The aim of the present study was to evaluate the expression patterns of selected SOXB proteins in the SGZ, of 8-week-old male and female 5xFAD mice, which represent a transgenic model of AD with a severe and very early development of amyloid pathology...
August 3, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/30102844/dual-targeting-combining-costimulation-blockade-and-bortezomib-to-permit-kidney-transplantation-in-sensitized-recipients
#15
Christopher K Burghuber, Miriam Manook, Brian Ezekian, Adriana C Gibby, Frank V Leopardi, Minqing Song, Jennifer Jenks, Frances Saccoccio, Sallie Permar, Alton B Farris, Neal N Iwakoshi, Jean Kwun, Stuart J Knechtle
Previous evidence suggests that a homeostatic germinal center (GC) response may limit bortezomib desensitization therapy. We evaluated the combination of costimulation blockade with bortezomib in a sensitized non-human primate kidney transplantation model. Sensitized animals were treated with bortezomib, belatacept and anti-CD40 mAb twice weekly for a month (n=6) and compared to control animals (n=7). Desensitization therapy mediated DSA reductions approached statistical significance (p=0.07) and significantly diminished bone marrow PCs, lymph node follicular helper T cells, and memory B cell proliferation...
August 13, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30102786/vivax-infection-alters-peripheral-b-cell-profile-and-induces-persistent-serum-igm
#16
Mandar Patgaonkar, Fabien Herbert, Krushali Powale, Prajakta Gandhe, Nithya Gogtay, Urmila Thatte, Sylviane Pied, Shobhona Sharma, Sulabha Pathak
B cell-mediated humoral responses are essential for controlling malarial infection. Studies have addressed the effects of Plasmodium falciparum infection on peripheral B cell subsets but not much is known for P. vivax infection. Furthermore, majority of the studies investigate changes during acute infection, but not after parasite clearance. In this prospective study we analyzed peripheral B cell profiles and antibody responses during acute P. vivax infection and upon recovery (30 days post-treatment) in a low-transmission area in India...
August 13, 2018: Parasite Immunology
https://www.readbyqxmd.com/read/30097219/innovative-approaches-to-track-lymph-node-germinal-center-responses-to-evaluate-development-of-broadly-neutralizing-antibodies-in-human-hiv-vaccine-trials
#17
M Patricia D'Souza, Mary A Allen, Jane A G Baumblatt, Cesar Boggiano, Shane Crotty, Christine Grady, Colin Havenar-Daughton, Antje Heit, Dale J Hu, Nina Kunwar, M Juliana McElrath
Phase 1 clinical studies will soon evaluate novel HIV-1 envelope immunogens targeting distinct 'germline' and memory B cell receptors to ultimately elicit HIV-1 broadly neutralizing antibodies (bNAbs). The National Institute of Allergy and Infectious Diseases (NIAID) recently convened a panel of US-based expert scientists, clinicians, sponsors and ethicists to discuss the role of sampling draining lymph nodes within preventive HIV vaccine trials. The meeting addressed the importance of evaluating germinal center (GC) responses following immunization to predict bNAb potency and breadth, and reviewed key aspects of this procedure within the clinical research setting, including informed consent, adverse event monitoring, study participant acceptability, medical expertise and training...
August 7, 2018: Vaccine
https://www.readbyqxmd.com/read/30096650/donepezil-butylated-hydroxytoluene-bht-hybrids-as-anti-alzheimer-s-disease-agents-with-cholinergic-antioxidant-and-neuroprotective-properties
#18
Pei Cai, Si-Qiang Fang, Hua-Li Yang, Xue-Lian Yang, Qiao-Hong Liu, Ling-Yi Kong, Xiao-Bing Wang
The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A novel family of donepezil-butylated hydroxytoluene (BHT) hybrids were designed, synthesized and evaluated as multifunctional ligands against AD. The optimal compound 7d displayed a balanced multifunctional profile covering an intriguing acetylcholinesterase (AChE) inhibition (IC50, 0.075 μM for eeAChE and 0.75 μM for hAChE) and Monoamine oxidase B (MAO-B) inhibition (IC50 , 7...
August 4, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30094406/gut-and-liver-b-cells-of-common-clonal-origin-in-primary-sclerosing-cholangitis-inflammatory-bowel-disease
#19
Brian K Chung, Eva Kristine Klemsdal Henriksen, Kristin Kaasen Jørgensen, Tom H Karlsen, Gideon M Hirschfield, Evaggelia Liaskou
B cells express an antigen-specific B-cell receptor (BCR) and may contribute to liver inflammation by recognizing shared antigens in the gut and liver. Herein, we used high-throughput BCR sequencing of the immunoglobulin heavy chain, specifically the complementarity-determining region 3 (CDR3), to characterize the B-cell repertoire of freshly-frozen paired gut and liver tissue samples from patients with primary sclerosing cholangitis (PSC) and concurrent inflammatory bowel disease (IBD) (PSC-IBD, n = 10) and paired formalin-fixed paraffin-embedded (FFPE) tumor-adjacent normal colon and liver tissue from patients with colorectal liver metastases (controls, n = 10)...
August 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30093532/b-cell-adaptor-for-pi3-kinase-bcap-modulates-cd8-effector-and-memory-t-cell-differentiation
#20
Mark D Singh, Minjian Ni, Jenna M Sullivan, Jessica A Hamerman, Daniel J Campbell
CD8+ T cells respond to signals via the T cell receptor (TCR), costimulatory molecules, and immunoregulatory cytokines by developing into diverse populations of effector and memory cells. The relative strength of phosphoinositide 3-kinase (PI3K) signaling early in the T cell response can dramatically influence downstream effector and memory T cell differentiation. We show that initial PI3K signaling during T cell activation results in up-regulation of the signaling scaffold B cell adaptor for PI3K (BCAP), which further potentiates PI3K signaling and promotes the accumulation of CD8+ T cells with a terminally differentiated effector phenotype...
August 9, 2018: Journal of Experimental Medicine
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