Abstract:
:Antigen-specific CD8 suppressor T cells (CD8(+) Ts) are adaptive regulatory T cells that are induced in vivo and in vitro by chronic antigenic stimulation of human T cells. CD8(+) Ts induce the upregulation of the inhibitory receptors ILT3 and ILT4 on monocytes and dendritic cells rendering these antigen presenting cells (APCs) tolerogenic. Tolerogenic APCs induce CD4(+) T helper anergy and elicit the differentiation of CD4(+) and CD8(+) T regulatory/suppressor cells. Overexpression of membrane ILT3 in APC results in inhibition of NF-κB activation, transcription of inflammatory cytokines and costimulatory molecules. Soluble ILT3-Fc which contains only the extracellular, Ig-like domain linked to mutated IgG1 Fc, is strongly immunosuppressive. ILT3-Fc, induces the differentiation of human CD8(+) Ts which inhibit CD4(+) Th and CD8(+) CTL effector function both in vitro and in vivo. The acquisition of Ts' function by primed CD8(+) T cells treated with ILT3-Fc was demonstrated to be the effect of the significant upregulation of BCL6, a transcriptional repressor of IL-2, IFN-gamma, IL-5 and granzyme B. The upregulated expression of BCL6, SOCS1 and DUSP10 is integral to the signature of ILT3-Fc-induced CD8(+) Ts. These genes are known inhibitors of cytokine production and TCR signaling and are targeted by miRNAs which are suppressed by ILT3-Fc. ILT3-Fc induces tolerance to allogeneic human islets and reverses rejection after its onset in a humanized NOD/SCID mouse model. Based on these findings we postulate that ILT3-Fc may become an important new agent for treatment of autoimmunity and transplant rejection.
journal_name
Exp Mol Patholjournal_title
Experimental and molecular pathologyauthors
Vlad G,Suciu-Foca Ndoi
10.1016/j.yexmp.2012.09.011subject
Has Abstractpub_date
2012-12-01 00:00:00pages
294-301issue
3eissn
0014-4800issn
1096-0945pii
S0014-4800(12)00133-5journal_volume
93pub_type
杂志文章abstract::Fine-needle aspiration biopsy remains the mainstay for preoperative examination of thyroid nodules; however, it does not provide a definite diagnosis in up to 25% of nodules. Considerable studies have been performed to identify molecular markers to resolve this diagnostic dilemma. The aim of this study was to establis...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2014.08.005
更新日期:2014-10-01 00:00:00
abstract::The reparative reaction is considered to be important during the occurrence of collapse in the femoral head with osteonecrosis (ONFH), but little is known about the long-term reparative process. The aim of this study was to determine and analyze the altered microRNA expression profile in the reparative interface of ON...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2015.01.002
更新日期:2015-04-01 00:00:00
abstract::Previously, we described an orthotopic cholangiocarcinoma model based on bile duct inoculation of spontaneously-transformed low grade malignant rat BDE1 cholangiocytes (BDEsp cells) compared to high grade malignant erbB-2/neu- transformed BDE1 cholangiocytes (BDEneu cells) into the livers of syngeneic rats, which clos...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2010.08.007
更新日期:2010-12-01 00:00:00
abstract::Esophageal squamous cell carcinoma (ESCC) is highly fatal due to late diagnosis and inefficient treatment. Early disease detection could improve diagnosis and patient survival. Esophageal squamous epithelial cells express SPRR3, a member of the small proline-rich protein family, which is downregulated in ESCC. Therefo...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2011.06.006
更新日期:2011-10-01 00:00:00
abstract::The relative resistance of fibroblasts to hypoxia and their remarkable adaptive plasticity in response to rapid changes in local tissue microenvironment made interstitial cardiac fibroblasts to be a key player in post-myocardial infarction myocardial repair. Cardiac fibroblasts are abundantly presented in the intersti...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章,评审
doi:10.1016/j.yexmp.2016.09.002
更新日期:2016-10-01 00:00:00
abstract::The aim of this study was to evaluate if polymorphisms of APLN and APLNR genes may play a role as susceptibility markers for hypertension in a group of Mexican-Mestizo patients. A case-control study was carried out including normotensive and hypertensive individuals. For these, two polymorphisms of APLN (rs3761581 and...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2016.07.007
更新日期:2016-08-01 00:00:00
abstract::We used the intragastric feeding rat model for alcoholic liver disease to evaluate the relationship among intercellular adhesion molecule-1 (ICAM-1) expression, tumor necrosis factor-alpha (TNF-alpha), plasma endotoxin, and inflammatory changes in the liver. Rats were fed different dietary fats (saturated fat, corn oi...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1006/exmp.1995.1005
更新日期:1995-02-01 00:00:00
abstract::The components of the insulin-like growth factor (IGF) system and molecules with which they interact are associated with the neoplastic transformation of cells in colorectal cancer. The IGF-binding protein-2 (IGFBP-2) plays a significant role in mitotic stimulation of the cancer cells and its concentration is signific...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2013.11.006
更新日期:2014-02-01 00:00:00
abstract::The parent-into-F1 mouse model (P-->F1) of acute graft-vs.-host disease (GVHD) is a useful model of human acute GVHD because it allows the study of the T cell contribution to pathology without the complicating effects of conditioning regimens. To determine the similarity of this model to human GVHD, we assessed injury...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2005.03.007
更新日期:2005-10-01 00:00:00
abstract::In this comparative study, rat hearts were perfused at 37 degrees C with three clearly defined protocols: the Ca2+ paradox, the O(2) paradox, and with 20 mM caffeine. Each protocol involved an initial priming (Ca(2+)(0) depletion or anoxia; stage 1) and subsequent full activation (Ca(2+)(0) repletion, caffeine or reox...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1006/exmp.1999.2275
更新日期:1999-10-01 00:00:00
abstract::As the fifth most common cancer and the second leading cause of cancer related deaths worldwide, hepatocellular carcinoma (HCC) causes up to one million deaths annually. Alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH) are becoming the two major risk factors because both may develop liver fibro...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2019.04.002
更新日期:2019-06-01 00:00:00
abstract::Previous studies demonstrated that more electronegative low density lipoprotein (LDL) isolated from human blood by ion exchange chromatography has a chemical composition and physical properties similar to desialylated LDL obtained by lectin chromatography (Avogaro et al., 1988; Orekhov et al., 1989). In this study, si...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1006/exmp.1995.1018
更新日期:1995-06-01 00:00:00
abstract::The CXC chemokine receptor CXCR4 was the first molecule identified as a coreceptor working in conjunction with CD4 to mediate cellular entry for the human immunodeficiency virus (HIV-1). Since that original discovery, 11 other seven-mtransmembrane domain molecules, many of which are chemokine receptors, have been show...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1006/exmp.2000.2336
更新日期:2000-12-01 00:00:00
abstract::The N-methyl-D-aspartate receptor (NMDAR), which is one of the glutamate receptors, is considered to have a close relationship to synaptic plasticity in the developing brain. In addition, it is known that the excessive stimulation of NMDARs can trigger neuronal apoptosis. In this study, we examined the distribution of...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/s0014-4800(03)00030-3
更新日期:2003-08-01 00:00:00
abstract::Meningiomas are among the most common tumors of the adult central nervous system (CNS). They are classified by the World Health Organization into three pathologic grades with increasing severity: grade I are benign with favorable treatment outcomes and low recurrence rates while grade III display malignant behavior an...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2018.10.007
更新日期:2018-12-01 00:00:00
abstract::Selected estimates of lipid peroxidation were analyzed in mouse quadriceps femoris muscle immediately after submaximal prolonged (9 hr) and exhaustive maximal running (2-3 hr), and at intervals 1-10 days afterward during the exercise-induced myopathy. Immediately after the two types of exertion no significant changes ...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/0014-4800(83)90077-1
更新日期:1983-06-01 00:00:00
abstract::Fluoride is known to cause ectopic calcification. The biochemical mechanism(s) involved in the initiation of calcification is not understood and the accompanying ultrastructural changes remain to be elucidated. Therefore, certain relevant parameters have been investigated in the aorta of rabbits administered fluoride,...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/0014-4800(90)90025-9
更新日期:1990-08-01 00:00:00
abstract::Paraoxonase gene polymorphisms (PON1-55 and PON1-192) were determined in four Mexican populations (Mestizos, Nahuas, Teenek and Mayos) belonging to different ethnic groups. The role of these polymorphisms in the lipid profile in the Mestizo group was also analyzed. PON1 polymorphisms were determined by polymerase chai...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2005.05.006
更新日期:2006-02-01 00:00:00
abstract::Host immune status is an important determinant of disease progression. Infections in the genital tract may alter the immunity in the particular site and hence affect the production of local cytokines. We performed this study to determine whether HIV in association with cervical HPV and CT/GC infections influences the ...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2008.10.001
更新日期:2009-02-01 00:00:00
abstract::Carbon tetrachloride-mediated loss of cytochrome P-450 has been compared in hepatic microsomes from untreated and phenobarbital-treated rats. At concentrations of carbon tetrachloride greater than 2.5 mM, a direct effect (i.e., NADPH- independent) on cytochrome P-450 was observed. This apparently arose from the "solve...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/0014-4800(86)90045-6
更新日期:1986-06-01 00:00:00
abstract::Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by loss of dopaminergic neurons in the substantia nigra. Recently, microRNAs (miRNAs) were emerging as important mediators in dopaminergic neuron biology. This study determined miR-410 expression in the 6-hydroxydopamine (6-OHDA)-induced in ...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2019.05.002
更新日期:2019-08-01 00:00:00
abstract::CD44 is a polymorphic family of immunologically related integral membrane glycoproteins associated with cell matrix adhesion, lymphocyte activation and targeting, and tumor growth and metastasis. We studied CD44 expression in 114 formalin-fixed paraffin-embedded thyroid tumors using the A3D8 anti-human CD44 monoclonal...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1006/exmp.1994.1037
更新日期:1994-12-01 00:00:00
abstract::Oral cancer is a major health problem in many parts of the world including India. The molecular mechanisms involved in oral tumorigenesis are not completely understood. Although surgery continues to be the most common treatment modality for this cancer, survival rates of oral cancer patients have still not significant...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2006.05.001
更新日期:2006-10-01 00:00:00
abstract::Ameloblastoma is a benign odontogenic neoplasm that may exhibit aggressive biological behavior as evidenced by its rapid growth and significance recurrence rates following initial surgical resection. Currently, the only therapy for ameloblastoma is surgical, and adjunctive treatment modalities are needed to mitigate t...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章,评审
doi:10.1016/j.yexmp.2014.09.001
更新日期:2014-12-01 00:00:00
abstract::Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative diseases of man and animals and are transmitted by a filterable pathogen whose identity is currently unresolved. Our data indicates that Spiroplasma, a wall-less bacterium, is involved in the pathogenesis of TSE. We searched for Spiroplasma ri...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2004.02.002
更新日期:2004-08-01 00:00:00
abstract::Lumican is a member of a small leucine-rich proteoglycan (SLRP) family and it regulates the assembly and diameter of collagen fibers in the extracellular matrix of various tissues. Lumican expression was reported in various kinds of tumor cells. Lumican inhibits the growth of melanoma cells, but the lumican in pancrea...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2010.01.010
更新日期:2010-06-01 00:00:00
abstract::We have analyzed the localization of dendritic cells (DCs) in non-lesional gray matter (NLGM) in comparison to non-lesional white matter (NLWM) and acute or chronic active multiple sclerosis (MS) lesions. Immunohistochemistry was performed on cryostat sections for DCs markers (CD209, CD205, CD83) and other markers for...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2007.05.006
更新日期:2007-10-01 00:00:00
abstract::Recently it was observed that the hypothyroid state induced by propylthiouracil treatment reduced the elimination rate of ethanol. This was based on the fact that hypothyroid rats could only tolerate 10 g/kg/day of ethanol infusion over 24 h. Euthyroid rats tolerate 13 to 14 g/kg/day of ethanol infusion. In the presen...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1006/exmp.2001.2381
更新日期:2001-08-01 00:00:00
abstract::To investigate the role of N-acetylglucosaminyltransferases V (GnT-V) in the malignancy of human hepatocellular carcinoma (HCC), the GnT-V stably suppressed cell line HepG2 GnT-V/1564 was constructed from HepG2. The proliferation, migration, invasion, metastasis of HepG2 GnT-V/1564 was investigated both in vitro and i...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2012.01.011
更新日期:2012-08-01 00:00:00
abstract::Currently there is critical need for the identification of reliable biomarkers to help guide clinical management of multiple sclerosis (MS) patients. We investigated the combined roles of Response Gene to Complement 32 (RGC-32), FasL, CDC2, AKT, and IL-21 as possible biomarkers of relapse and response to glatiramer ac...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2015.09.007
更新日期:2015-12-01 00:00:00