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K W Lee, B Choi, Y M Kim, C W Cho, H Park, J I Moon, G-S Choi, J B Park, S J Kim
BACKGROUND: Although the induction of mixed allogeneic chimera shows promising clinical tolerance results in organ transplantation, its clinical relevance as an anti-cancer therapy is yet unknown. We introduced a mixed allogenic chimera setting with the use of a murine colon cancer cell line, CT26, by performing double bone marrow transplantation. METHODS: We analyzed donor- and recipient-restricted anti-cancer T-cell responses, and phenotypes of subpopulations of T cells...
June 2017: Transplantation Proceedings
Amanda C Lyons, Matthew J Hoostal, Juan L Bouzat
The major histocompatibilty complex (MHC) has become increasingly important in the study of the immunocapabilities of non-model vertebrates due to its direct involvement in the immune response. The characterization of MHC class I loci in the lark sparrow (Chondestes grammacus) revealed multiple MHC class I loci with elevated genetic diversity at exon 3, evidence of differential selection between the peptide binding region (PBR) and non-PBR, and the presence of multiple pseudogenes with limited divergence. The minimum number of functional MHC class I loci was estimated at four...
August 2015: Genetica
Séverine Ciré, Sylvie Da Rocha, Roseline Yao, Sylvain Fisson, Christian J Buchholz, Mary K Collins, Anne Galy
Gene transfer vectors such as lentiviral vectors offer versatile possibilities to express transgenic antigens for vaccination purposes. However, viral vaccines leading to broad transduction and transgene expression in vivo, are undesirable. Therefore, strategies capable of directing gene transfer only to professional antigen-presenting cells would increase the specific activity and safety of genetic vaccines. A lentiviral vector pseudotype specific for murine major histocompatibilty complex class II (LV-MHCII) was recently developed and the present study aims to characterize the in vivo biodistribution profile and immunization potential of this vector in mice...
2014: PloS One
Michael J Pokrass, Monica F Liu, Margaret A Lindorfer, Ronald P Taylor
β₂-Microglobulin (β2M), the light chain of the class I major histocompatibilty complex (MHC-I), is a promising tumor target for monoclonal antibodies (mAbs) in cancer immunotherapy. Several reports indicate that chelation of cell-associated β2M by specific mouse mAbs promotes tumor cell destruction by inducing apoptosis or other cytotoxic signaling pathways. Human mAbs employed in cancer therapy are usually IgG1, which mediates cell-killing by effector mechanisms including complement dependent cytotoxicity (CDC)...
December 2013: Molecular Immunology
H T Celik, S Abusoglu, S F Burnik, S Sezer, M A Serdar, M Ercan, N Uguz, M Avcikucuk, Bal Ceylan, M Yildirimkaya
OBJECTIVE: Interleukin-33 (IL-33), a 30 kDa cytokine, is a member of IL-1 family. It is considered to be an autoimmune biomarker associated with T helper 2 (Th 2) response. γ-interferon is also produced by T helper 1 (Th 1) cells to induce cellular responses. γ-interferon is a 143-amino acid residue glycoprotein with several biological functions including potent anti-viral activity, stimulation of macrophage activity, modulation of Major Histocompatibilty Complex class I/class II expression, and regulation of a diversity of specific immune responses...
April 2013: Endocrine Regulations
Ulrich H Weidle, Britta Schneider, Guy Georges, Ulrich Brinkmann
In this review, we summarize approaches to treat cancer with genetically engineered fusion proteins. Such proteins can act as decoy receptors for several ligands or as recruiters of immune effector cells to tumor. Examples of interference with growth factor-mediated tumor growth and tumor-related angiogenesis with fusion proteins consisting of the extracellular domains, and in some cases also of entities of one or several receptors and the Fc part of human IgG1, are discussed. In addition, we present strategies for recruitment of immune effector cells to tumor with fusion proteins...
November 2012: Cancer Genomics & Proteomics
Yosra Ben Othmane, Ezzeddine Ghazouani, Amel Mezlini, Awatef Lagha, Mejda Raïs, Radhia Kochkar, Sabrina Zidi, Mehdi Afrit, Luisa Mota-Vieira, Besma Yacoubi Loueslati
The variability in host immunogenetic background, especially in human major histocompatibilty genes, has been shown to influence the susceptibility to human papillomavirus (HPV) infection and cervical neoplasia. Here, we conducted a case-control study in Tunisian women to examine the effect of genetic variation in HLA class II DRB1 and DQB1 genes on invasive cervical cancer (ICC) and squamous cell carcinoma (SCC). HLA genotyping was performed by PCR sequence-specific primers technique. The data revealed significant positive and negative associations, suggesting either predisposing or protective effects of these genes in the disease outcome...
September 2012: Bulletin du Cancer
Sabine Tischer, Till Kaireit, Constança Figueiredo, Oliver Hiller, Britta Maecker-Kolhoff, Renè Geyeregger, Stephan Immenschuh, Rainer Blasczyk, Britta Eiz-Vesper
Multimers of soluble peptide-major histocompatibilty complex (pMHC) molecules are used in both basic and clinical immunology. They allow the specific visualization and isolation of antigen-specific T cells from ex vivo samples. Adoptive transfer of antigen-specific T cells sorted by pMHC multimers is an effective strategy for treatment of patients with malignancies or infectious diseases after transplantation. We developed a new reversible pMHC multimer called 'Histamer' to enable the specific detection and isolation of antiviral T cells from peripheral blood...
September 2012: International Immunology
M P De Miguel, S Fuentes-Julián, A Blázquez-Martínez, C Y Pascual, M A Aller, J Arias, F Arnalich-Montiel
Mesenchymal stem cells (MSCs) have been isolated from a variety of tissues, such as bone marrow, skeletal muscle, dental pulp, bone, umbilical cord and adipose tissue. MSCs are used in regenerative medicine mainly based on their capacity to differentiate into specific cell types and also as bioreactors of soluble factors that will promote tissue regeneration from the damaged tissue cellular progenitors. In addition to these regenerative properties, MSCs hold an immunoregulatory capacity, and elicit immunosuppressive effects in a number of situations...
June 2012: Current Molecular Medicine
Tyler S Cole, Min Zhang, Theodore J Standiford, Michael Newstead, Jay Luther, Jiajie Zhang, Chun-Chia Chen, John Y Kao
BACKGROUND: As essential components of the innate immune system, dendritic cells (DCs) can interact directly with pathogens as well as participate in the adaptive immune response. In cells closely related to DCs such as macrophages and monocytes, prior exposure to minute amounts of endotoxin can lead to a refractory period where subsequent exposure to higher doses fails to induce an inflammatory response; little research has investigated this effect on DCs. This study tested if murine bone marrow-derived dendritic cells (BM-DCs) respond to endotoxin- and bacterial sonicate-induced tolerance by decreased inflammatory and increased anti-inflammatory response, and the role of IRAK-M, an intracellular negative regulator of TLR signaling, in this tolerance...
May 30, 2012: Immunology Letters
Jon J van Rood, Andromachi Scaradavou, Cladd E Stevens
During pregnancy women can develop B- and T-cell immunity against the inherited paternal antigens (IPAs) of the fetus, such as HLA, peptides of minor histocompatibilty antigens, and possibly onco-fetal antigens. The biological and pathological role of these pregnancy-induced immunological events is only understood in part. However, anti-IPA immunity in the mother persists for many decades after delivery and may reduce relapse in offspring with leukemia after HLA-haploidentical transplantation of maternal hematopoietic stem cells (HSC)...
February 14, 2012: Proceedings of the National Academy of Sciences of the United States of America
Priya Londhe, Bo Zhu, Jinu Abraham, Charles Keller, Judith Davie
Rhabdomyosarcomas (RMS) are highly malignant pediatric sarcomas. We have discovered that the gene encoding the major histocompatibilty complex class II transactivator, CIITA, is silenced in cells representing both major subtypes of RMS. Silencing of CIITA prevents the IFN-γ inducible expression of MHC class II genes in these cells. Overexpression of CIITA in these cells can restore MHC expression. We have found that IFN-γ signaling is intact in these cells, but pSTAT1 and IRF1 do not bind to the CIITA PIV promoter...
August 15, 2012: International Journal of Cancer. Journal International du Cancer
Nikolay Turovets, Jeffrey Fair, Richard West, Alina Ostrowska, Ruslan Semechkin, Jeffrey Janus, Li Cui, Vladimir Agapov, Irina Turovets, Andrey Semechkin, Marie Csete, Larissa Agapova
Human parthenogenetic stem cells (hpSCs) are pluripotent stem cells with enormous potential as cell sources for cell-based therapies: hpSCs may have histocompatibilty advantages over human embryonic stem cells (hESCs) and derivation of hpSCs does not require viable blastocyst destruction. For translation of all pluripotent stem cell-based therapies, derivation of differentiated cell products that are not contaminated with undifferentiated cells is a major technical roadblock. We report here a novel method to derive high-purity definitive endoderm (DE) from hpSCs, based on reproducing features of the normal human embryonic microenvironment...
2012: Cell Transplantation
K T Coppieters, N Amirian, M G von Herrath
Apoptosis is known as a major mechanism which contributes to beta cell decay in type 1 diabetes. Commitment to this pathway generally involves caspase-mediated protein cleavage and was found to induce cross-presentation of a specific antigen repertoire under certain inflammatory conditions. We aimed to assess the significance of the CD8 T cell population reactive against such caspase-cleaved apoptotic self-antigens in pancreatic islets of prediabetic human leucocyte antigen (HLA)-A2 transgenic non-obese diabetic chimeric monochain transgene construct (NOD...
August 2011: Clinical and Experimental Immunology
Julia Yuen Shan Tsang, Daxu Li, Derek Ho, Jiao Peng, Aimin Xu, Jonathan Lamb, Yan Chen, Paul Kwong Hang Tam
Adiponectin (ADN) is an adipocytokine with anti-inflammatory properties. Although it has been reported that ADN can inhibit the immunostimulatory function of monocytes and macrophages, little is known of its effect on dendritic cells (DC). Recent data suggest that ADN can regulate immune responses. DCs are uniquely specialised antigen presenting cells that play a central role in the initiation of immunity and tolerance. In this study, we have investigated the immuno- modulatory effects of ADN on DC functions...
May 2011: International Immunopharmacology
Nidal Muhanna, Lina Abu Tair, Sarit Doron, Johnny Amer, Maysa Azzeh, Mahmud Mahamid, Scott Friedman, Rifaat Safadi
BACKGROUND AND AIMS: Interactions between hepatic stellate cells (HSCs) and immune cell subsets have emerged as important determinants of liver fibrosis progression and regression. Natural killer (NK) cells have an antifibrotic activity through killing of activated HSCs. In liver injury NK cell expression of activating/inhibitory killer immunoglobulin-related receptors (aKIR/iKIR) and their ratio are significantly increased, while class I major histocompatibilty (MHC) expression by activated HSCs is decreased...
January 2011: Gut
E T Mee, N Berry, C Ham, A Aubertin, J Lines, J Hall, R Stebbings, M Page, N Almond, N J Rose
The restricted major histocompatibilty complex of Mauritian cynomolgus macaques confers exceptional potential on this species in human immunodeficiency virus (HIV) vaccine development. However, knowledge of the effects of Mhc genetics on commonly used simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) stocks is incomplete. We determined the effect of Mhc haplotypes on SHIVsbg replication kinetics in a cohort of 25 naïve cynomolgus macaques. Haplotype M3 was associated with a 1...
September 2010: Tissue Antigens
Olivia I Koues, Ninad T Mehta, Agnieszka D Truax, R Kyle Dudley, Jeanne K Brooks, Susanna F Greer
BACKGROUND: Studies indicate that the 19S proteasome contributes to chromatin reorganization, independent of the role the proteasome plays in protein degradation. We have previously shown that components of the 19S proteasome are crucial for regulating inducible histone activation events in mammalian cells. The 19S ATPase Sug1 binds to histone-remodeling enzymes, and in the absence of Sug1, a subset of activating epigenetic modifications including histone H3 acetylation, H3 lysine 4 trimethylation and H3 arginine 17 dimethylation are inhibited at cytokine-inducible major histocompatibilty complex (MHC)-II and class II transactivator (CIITA) promoters, implicating Sug1 in events required to initiate mammalian transcription...
2010: Epigenetics & Chromatin
M Dumonceaux, C Knoop, B Rondelet, M Estenne
In 2009 lung transplantation is a valuable therapeutic option for a spectrum of end-stage pulmonary diseases. To many patients who are dying, lung transplantation offers a new and normal life for several years. However, lung transplantation is a major surgical intervention associated with a significant early mortality. Moreover, matching according to the major human histocompatibilty antigens is impossible, exposing the recipient to an increased risk of acute and chronic rejection. Chronic rejection and its clinical corollary the bronchiolitis obliterans syndrome, is the main cause of death medium and long term...
June 2009: Revue des Maladies Respiratoires
Evan W Newell, Lawrence O Klein, Wong Yu, Mark M Davis
The direct detection of antigen-specific T cells using tetramers of soluble peptide-major histocompatibilty complex (pMHC) molecules is widely used in both basic and clinical immunology. However, the number of specificities that can be assessed simultaneously has been a major limitation. Here we describe and validate a method using combinations of fluorescent pMHC tetramers to simultaneously detect and enrich for many (>or=15) T-cell specificities in a single human blood sample.
July 2009: Nature Methods
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