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https://www.readbyqxmd.com/read/29156204/autologous-hematopoietic-cell-transplantation-for-adult-acute-myeloid-leukemia-an-obsolete-or-resurfacing-concept
#1
REVIEW
Hillard M Lazarus, Najla El Jurdi
Improving long-term outcomes of adult acute myeloid leukemia (AML) patients remains a challenge. Major scientific and clinical advances have led to a better understanding of the disease biology, and the majority of patients achieve a complete remission (CR) after induction therapy. Relapse risk, however, remains considerable and is the leading cause of death in this patient population. Significant efforts to improve outcomes emphasize use of post-remission therapies such as hematopoietic cell transplantation (HCT), an increasingly utilized modality...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29155844/hypoxia-and-hypoxia-inducible-factor-hif-downregulate-antigen-presenting-mhc-class-i-molecules-limiting-tumor-cell-recognition-by-t-cells
#2
Shalini Sethumadhavan, Murillo Silva, Phaethon Philbrook, Thao Nguyen, Stephen M Hatfield, Akio Ohta, Michail V Sitkovsky
Human cancers are known to downregulate Major Histocompatibility Complex (MHC) class I expression thereby escaping recognition and rejection by anti-tumor T cells. Here we report that oxygen tension in the tumor microenvironment (TME) serves as an extrinsic cue that regulates antigen presentation by MHC class I molecules. In support of this view, hypoxia is shown to negatively regulate MHC expression in a HIF-dependent manner as evidenced by (i) lower MHC expression in the hypoxic TME in vivo and in hypoxic 3-dimensional (3D) but not 2-dimensional (2D) tumor cell cultures in vitro; (ii) decreased MHC in human renal cell carcinomas with constitutive expression of HIF due to genetic loss of von Hippel-Lindau (VHL) function as compared with isogenically paired cells with restored VHL function, and iii) increased MHC in tumor cells with siRNA-mediated knockdown of HIF...
2017: PloS One
https://www.readbyqxmd.com/read/29153131/donor-sirp-%C3%AE-polymorphisms-widening-the-innate-to-adaptive-continuum-in-allograft-rejection
#3
Madhav C Menon, Peter S Heeger
In the usual paradigm, self:nonself recognition is attributed to calls of the adaptive immune system, owing to variations in specialized genes encoded within the major histocompatibility complex loci. However, an increasing body of data has shown that cells of the innate immune system also have self:nonself recognition functions relevant to organ transplantation, and this trait may derive from genes located outside the major histocompatibility complex loci. A recent publication identifies the donor SIRP-α gene as a non-major histocompatibility complex locus responsible for nonself recognition by monocytes, with variability resulting in changes in the surface interaction of SIRP-α with its ligand CD47...
December 2017: Kidney International
https://www.readbyqxmd.com/read/29152228/cd1-from-molecules-to-diseases
#4
REVIEW
D Branch Moody, Sara Suliman
The human cluster of differentiation (CD)1 system for antigen display is comprised of four types of antigen-presenting molecules, each with a distinct functional niche: CD1a, CD1b, CD1c, and CD1d. Whereas CD1 proteins were thought solely to influence T-cell responses through display of amphipathic lipids, recent studies emphasize the role of direct contacts between the T-cell receptor and CD1 itself. Moving from molecules to diseases, new research approaches emphasize human CD1-transgenic mouse models and the study of human polyclonal T cells in vivo or ex vivo in disease states...
2017: F1000Research
https://www.readbyqxmd.com/read/29151514/a-case-of-dermatomyositis-complicated-by-digital-ischemia-and-lung-adenocarcinoma-in-a-patient-with-positive-anti-signal-recognition-particle-antibodies
#5
Takashi Nawata, Makoto Kubo, Hitomi Mitsui, Keiji Oishi, Masatoshi Omoto, Takashi Kanda, Masafumi Yano
A 58-year-old Japanese woman was diagnosed with anti-signal recognition particle (SRP)-positive dermatomyositis associated with Sjögren's syndrome, rheumatoid arthritis and lung adenocarcinoma. She presented with cutaneous lesions, including ulceration of her right middle finger. Tissue specimens obtained from her right deltoid muscle were positive for CD4(+) T-cell infiltration and the sarcolemma showed the upregulation of major histocompatibility complex (MHC) class I antigens. The present case suggests that overlapping autoimmune diseases or complications of malignancy may result in an atypical clinical presentations and histological findings in patients with anti-SRP antibody-positive dermatomyositis...
November 20, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29151033/induction-of-dendritic-cell-mediated-activation-of-t-cells-from-atherosclerotic-plaques-by-human-heat-shock-protein-60
#6
Mizanur Rahman, Johnny Steuer, Peter Gillgren, Assim Hayderi, Anquan Liu, Johan Frostegård
BACKGROUND: Atherosclerosis is characterized by the presence of activated immune-competent cells including dendritic cells (DCs) and T cells, dead cells, and oxidized low-density lipoprotein. HSP60 (Heat shock protein 60) has been implicated in atherosclerosis. A plasma protein, Annexin A5, has atheroprotective properties. METHODS AND RESULTS: Human DCs differentiated from peripheral blood monocytes were treated with human HSP60 or HSP90 and autologous T cells were cocultured with these pretreated DCs (mDCs)...
November 18, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29150238/a-t-cell-receptor-locus-harbors-a-malaria-specific-immune-response-gene
#7
Natalija Van Braeckel-Budimir, Stephanie Gras, Kristin Ladell, Tracy M Josephs, Lecia Pewe, Stina L Urban, Kelly L Miners, Carine Farenc, David A Price, Jamie Rossjohn, John T Harty
Immune response (Ir) genes, originally proposed by Baruj Benacerraf to explain differential antigen-specific responses in animal models, have become synonymous with the major histocompatibility complex (MHC). We discovered a non-MHC-linked Ir gene in a T cell receptor (TCR) locus that was required for CD8(+) T cell responses to the Plasmodium berghei GAP5040-48 epitope in mice expressing the MHC class I allele H-2D(b). GAP5040-48-specific CD8(+) T cell responses emerged from a very large pool of naive Vβ8...
November 10, 2017: Immunity
https://www.readbyqxmd.com/read/29148973/the-somatically-generated-portion-of-the-t-cell-receptor-cdr3%C3%AE-contributes-to-the-mhc-allele-specificity-of-the-t-cell-receptor
#8
Philippa Marrack, Sai Harsha Krovi, Daniel Silberman, Janice White, Eleanor Kushnir, Maki Nakayama, James Crooks, Thomas Danhorn, Sonia Leach, Randy Anselment, James Scott-Browne, Laurent Gapin, John Kappler
Mature T cells bearing αβ T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor β chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor α and β chain and, surprisingly, dramatically affected by the non germ line encoded portions of CDR3 of the T cell receptor α chain...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29141674/repair-of-articular-cartilage-and-subchondral-defects-in-rabbit-knee-joints-with-a-polyvinyl-alcohol-nano-hydroxyapatite-polyamide-66-biological-composite-material
#9
Tao Guo, Xiaobin Tian, Bo Li, Tianfu Yang, Yubao Li
BACKGROUND: This study sought to prepare a new PVA/n-HA/PA66 composite to investigate the repair of articular cartilage and subchondral defects in rabbit knee joints. METHODS: A 5 × 5 × 5 mm-sized defect was created in the patellofemoral joints of 72 healthy adult New Zealand rabbits. The rabbits were then randomly divided into three groups (n = 24): PVA/n-HA+PA66 group, polyvinyl alcohol (PVA) group, and control (untreated) group. Cylindrical PVA/n-HA+PA66, 5 × 5 mm, comprised an upper PVA layer and a lower n-HA+PA66 layer...
November 15, 2017: Journal of Orthopaedic Surgery and Research
https://www.readbyqxmd.com/read/29140228/co-factor-independent-phosphoglycerate-mutase-of-leishmania-donovani-modulates-macrophage-signalling-and-promotes-t-cell-repertoires-bearing-epitopes-for-both-mhc-i-and-mhc-ii
#10
Manish K Singh, Fauzia Jamal, Amit K Dubey, Pushkar Shivam, Sarita Kumari, Pushpanjali, Ghufran Ahmed, Manas R Dikhit, S Narayan, V N R DAS, Krishna Pandey, K K Sinha, P DAS, Shubhankar K Singh
Immunoactivation depends upon the antigen potential to modulate T-cell repertoires. The present study has enumerated the effect of 61 kDa recombinant Leishmania donovani co-factor-independent phosphoglycerate mutase (rLd-iPGAM) on mononuclear cells of healthy and treated visceral leishmaniasis subjects as well as on THP-1 cell line. rLd-iPGAM stimulation induced higher expression of interleukin-1β (IL-1β) in the phagocytic cell, its receptor and CD69 on T-cell subsets. These cellular activations resulted in upregulation of host-protective cytokines IL-2, IL-12, IL-17, tumour necrosis factor-α and interferon-γ, and downregulation of IL-4, IL-10 and tumour growth factor-β...
November 15, 2017: Parasitology
https://www.readbyqxmd.com/read/29134258/novel-full-length-major-histocompatibility-complex-class-i-allele-discovery-and-haplotype-definition-in-pig-tailed-macaques
#11
Matthew R Semler, Roger W Wiseman, Julie A Karl, Michael E Graham, Samantha M Gieger, David H O'Connor
Pig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to that of rhesus and cynomolgus macaques...
November 13, 2017: Immunogenetics
https://www.readbyqxmd.com/read/29133251/immune-response-of-interferon-%C3%AE-inducible-lysosomal-thiol-reductase-gilt-from-chinese-sturgeon-acipenser-sinensis-to-microbial-invasion-and-its-antioxdative-activity-in-lipopolysaccharides-treated-mammalian-dentritic-cells
#12
Xiuling You, Liu Liu, Xiuyu Li, Hejun Du, Dongsong Nie, Xingguo Zhang, Haibing Tong, Mingjiang Wu, Yitian Gao, Zhiyong Liao
Interferon-γ-inducible lysosomal thiol reductase (GILT) plays an important role in the major histocompatibility complex-restricted antigen processing of endocytosed proteins via catalyzing the disulfide bond reduction in the endocytic pathway. Here, the cDNA of Chinese sturgeon (Acipenser sinensis) GILT (CsGILT) was cloned. It contained an open reading frame of 762 nucleotides encoding a protein of 254 amino acids with an estimated molecular weight of 28.1 kDa. The characteristic structural features, including a signature sequence CQHGX2ECX2NX4C, a CXXC motif, two potential N-glycosylation sites, and eight conserved cysteines were detected in the deduced amino acid sequence of CsGILT...
November 10, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29132473/-progress-in-clinical-studies-of-chimeric-antigen-receptor-engineered-t-cells-for-treatment-of-childhood-cancer
#13
Ya-Ru Ni, Xiao-Jun Xu, Yong-Min Tang
Nowadays, the 5-year survival rate of childhood cancer patients can be more than 80%, but some patients with relapse and refractory cancers have shown no good response to traditional strategies. Chimeric antigen receptor engineered T (CAR-T) cell therapy is promising for these patients. CAR-T cells recognize the tumor-associated antigens in a non-major histocompatibility complex-restricted manner, so their anti-tumor ability is enhanced. There are four generations of CAR-T cells now. The complete remission rate of pediatric patients with relapse and refractory acute lymphoblastic leukemia can be as high as 90% when treated with CD19-targeting CAR-T cells...
November 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29132293/genomic-regions-associated-with-host-response-to-porcine-reproductive-and-respiratory-syndrome-vaccination-and-co-infection-in-nursery-pigs
#14
Jenelle R Dunkelberger, Nick V L Serão, Ziqing Weng, Emily H Waide, Megan C Niederwerder, Maureen A Kerrigan, Joan K Lunney, Raymond R R Rowland, Jack C M Dekkers
BACKGROUND: The WUR1000125 (WUR) single nucleotide polymorphism (SNP) can be used as a genetic marker for host response to porcine reproductive and respiratory syndrome (PRRS), PRRS vaccination, and co-infection with porcine circovirus type 2b (PCV2b). Objectives of this study were to identify genomic regions other than WUR associated with host response to PRRS vaccination and PRRSV/PCV2b co-infection and regions with a different effect on host response to co-infection, depending on previous vaccination for PRRS...
November 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29132144/a-neoantigen-fitness-model-predicts-tumour-response-to-checkpoint-blockade-immunotherapy
#15
Marta Łuksza, Nadeem Riaz, Vladimir Makarov, Vinod P Balachandran, Matthew D Hellmann, Alexander Solovyov, Naiyer A Rizvi, Taha Merghoub, Arnold J Levine, Timothy A Chan, Jedd D Wolchok, Benjamin D Greenbaum
Checkpoint blockade immunotherapies enable the host immune system to recognize and destroy tumour cells. Their clinical activity has been correlated with activated T-cell recognition of neoantigens, which are tumour-specific, mutated peptides presented on the surface of cancer cells. Here we present a fitness model for tumours based on immune interactions of neoantigens that predicts response to immunotherapy. Two main factors determine neoantigen fitness: the likelihood of neoantigen presentation by the major histocompatibility complex (MHC) and subsequent recognition by T cells...
November 8, 2017: Nature
https://www.readbyqxmd.com/read/29131441/genetic-and-epigenetic-regulation-of-major-histocompatibility-complex-class-i-gene-expression-in-bovine-trophoblast-cells
#16
Bi Shi, Aaron J Thomas, Abby D Benninghoff, Benjamin R Sessions, Qinggang Meng, Parveen Parasar, Heloisa M Rutigliano, Kenneth L White, Christopher J Davies
PROBLEM: The regulatory mechanisms governing differential expression of classical major histocompatibility complex (MHC) class I (MHC-Ia) and non-classical MHC class I (MHC-Ib) genes are poorly understood. METHOD OF STUDY: Quantitative reverse transcription- polymerase chain reaction (PCR) was used to compare the abundance of MHC-I transcripts and related transcription factors in peripheral blood mononuclear cells (PBMC) and placental trophoblast cells (PTC). Methylation of MHC-I CpG islands was detected by bisulfite treatment and next-generation sequencing...
November 12, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29129831/identification-of-new-genetic-variants-of-hla-dqb1-associated-with-human-longevity-and-lipid-homeostasis-a-cross-sectional-study-in-a-chinese-population
#17
Fan Yang, Liang Sun, Xiaoquan Zhu, Jing Han, Yi Zeng, Chao Nie, Huiping Yuan, Xiaoling Li, Xiaohong Shi, Yige Yang, Caiyou Hu, Zeping Lv, Zezhi Huang, Chenguang Zheng, Siying Liang, Jin Huang, Gang Wan, Keyan Qi, Bin Qin, Suyan Cao, Xin Zhao, Yongqiang Zhang, Ze Yang
Healthy longevity has been an unremitting pursuit of human, but its genetic and the environment causes are still unclear. As longevity population is a good healthy aging model for understanding how the body begin aging and the process of aging, and plasma lipids metabolism and balance is a very important to life maintain and physiologic functional turnover. It is important to explore how the effect of genetic variants associated long-life individuals on lipids metabolism and balance. Therefore, we developed a comparative study based population which contains 2816 longevity and 2819 control...
November 10, 2017: Aging
https://www.readbyqxmd.com/read/29127683/gene-and-cell-therapy-for-%C3%AE-thalassemia-and-sickle-cell-disease-with-induced-pluripotent-stem-cells-ipscs-the-next-frontier
#18
Eirini P Papapetrou
In recent years, breakthroughs in human pluripotent stem cell (hPSC) research, namely cellular reprogramming and the emergence of sophisticated genetic engineering technologies, have opened new frontiers for cell and gene therapy. The prospect of using hPSCs, either autologous or histocompatible, as targets of genetic modification and their differentiated progeny as cell products for transplantation, presents a new paradigm of regenerative medicine of potential tremendous value for the treatment of blood disorders, including beta-thalassemia (BT) and sickle cell disease (SCD)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29126597/role-of-autophagy-in-mhc-class-i-restricted-antigen-presentation
#19
Luc Van Kaer, Vrajesh V Parekh, J Luke Postoak, Lan Wu
Major histocompatibility complex (MHC) class I molecules present peptide antigens to MHC class I-restricted CD8(+) T lymphocytes. The peptides loaded onto MHC class I molecules are typically derived from cytosolic antigens, which includes both self and foreign proteins. In addition to this classical MHC class I antigen presentation pathway, some cell types, especially dendritic cells can present antigens from exogenous sources to MHC class I-restricted CD8(+) T cells, in a process called cross-presentation...
November 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29125738/profiling-of-protein-o-glcnacylation-in-murine-cd8-effector-and-memory-like-t-cells
#20
Aime Lopez Aguilar, Yu Gao, Xiaomeng Hou, Gregoire Lauvau, John R Yates, Peng Wu
During an acute infection, antigenic stimulation leads to activation, expansion, and differentiation of naïve CD8(+) T cells, first into cytotoxic effector cells and eventually into long-lived memory cells. T cell antigen receptors (TCRs) detect antigens on antigen-presenting cells (APCs) in the form of antigenic peptides bound to major histocompatibility complex I (MHC-I)-encoded molecules and initiate TCR signal transduction network. This process is mediated by phosphorylation of many intracellular signaling proteins...
November 10, 2017: ACS Chemical Biology
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