Abstract：
:Inoculation of plasmid DNA is a simple way to immunize, but it is characterized by low immunogenicity, which has hampered the development of effective DNA vaccines for human use. Here, we discuss how poor immunogenicity can be solved and present our proposal: genetically programmed B lymphocytes as antigen-presenting cell (APC) vaccines. First, we demonstrate that mature B lymphocytes take up plasmid DNA spontaneously, i.e., in the absence of any facilitating molecule or event, spontaneous lymphocyte transgenesis. Second, we demonstrate that transgenic B lymphocytes are easily and reproducibly turned into functional APCs with dual characteristics: upregulation of costimulatory molecules and endogenous synthesis of antigen. Used as immunogens in mice, transgenic B lymphocytes induce robust and long-lasting T-cell immunity after single intravenous injection. Surprisingly, immunity and protection against lethal virus challenge can be obtained with a single intravenous injection of 3 x 10(2) transgenic lymphocytes. The new approach is discussed relative to the advantage of targeting secondary lymphoid organs with genetically programmed B lymphocytes and the advantage offered with respect to low antigen dose. We suggest that these properties reflect on simple characteristics, such as time synchronization and initial localization to secondary lymphoid organs of APCs endowed with protracted synthesis and presentation of antigen to T cells.
journal_name
Immunol Revjournal_title
Immunological reviewsauthors
Zanetti M,Castiglioni P,Rizzi M,Wheeler M,Gerloni Mdoi
10.1111/j.0105-2896.2004.00152.xkeywords:
subject
Has Abstractpub_date
2004-06-01 00:00:00pages
264-78eissn
0105-2896issn
1600-065Xpii
IMR152journal_volume
199pub_type
杂志文章,评审abstract：:Innate lymphoid cells (ILCs) constitute a family of effectors in innate immunity and regulators of tissue remodeling that have a cytokine and transcription factor expression pattern that parallels that of the T-helper (Th) cell family. Here, we discuss how ILCs can be categorized and summarize the current knowledge of...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12034
更新日期：2013-03-01 00:00:00
abstract：:Multiple myeloma (MM) is a tumor of long-lived bone marrow plasma cells (PCs). Nearly 40% of MM tumors have immunoglobulin H (IgH) translocations involving four recurrent chromosomal loci (oncogenes): 11q13 (cyclin D1), 6p21 (cyclin D3), 4p16 (MMSET and FGFR3), and 16q23 (c-maf). Other MM tumors have Ig translocations...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2003.00052.x
更新日期：2003-08-01 00:00:00
abstract：:Idiotypic networks, after being a dominating paradigm for more than a decade, have fallen out of fashion in parallel with the rapid success of molecular immunobiology. Today signs of a possible renaissance in idiotypic network studies are visible. For system biologists and also for physicists, the network idea remains...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2006.00496.x
更新日期：2007-04-01 00:00:00
abstract：:Highlights in a 4-decade exploration of lymphocyte differentiation begin with comparative studies in birds and mammals leading to recognition of the separate T- and B-cell differentiation pathways and their cooperative interaction. The global effects of aborting IgM B-cell development with anti-mu antibodies indicated...
journal_title：Immunological reviews
pub_type： 历史文章,杂志文章,评审
doi：10.1034/j.1600-065x.2002.18515.x
更新日期：2002-07-01 00:00:00
abstract：:Probabilistic modeling is fundamental to the statistical analysis of complex data. In addition to forming a coherent description of the data-generating process, probabilistic models enable parameter inference about given datasets. This procedure is well developed in the Bayesian perspective, in which one infers probab...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12664
更新日期：2018-07-01 00:00:00
abstract：:The precise mechanisms that govern memory T-cell lineage commitment during an immune response continue to be the subject of intense scrutiny. The existence of memory T-cell subsets defined by location, function, and phenotype adds an additional layer of complexity to the overall memory T-cell population. In this revie...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2006.00393.x
更新日期：2006-06-01 00:00:00
abstract：:The response to pathogens and damage in plants and animals involves a series of carefully orchestrated, highly evolved, molecular mechanisms resulting in pathogen resistance and wound healing. In metazoans, damage- or pathogen-associated molecular pattern molecules (DAMPs, PAMPs) execute precise intracellular tasks an...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2007.00579.x
更新日期：2007-12-01 00:00:00
abstract：:One of the fundamental aspects of the innate immune system is its capacity to discriminate between self and non-self or altered self, and to quickly respond by eliciting effector mechanisms that act in concert to restore normalcy. This capacity is determined by a set of evolutionarily conserved pattern recognition rec...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2011.01045.x
更新日期：2011-09-01 00:00:00
abstract：:Chronic inflammation in the tumor microenvironment and evasion of the antitumor effector immune response are two of the emerging hallmarks required for oncogenesis and cancer progression. The innate immune system not only plays a critical role in perpetuating these tumor-promoting hallmarks but also in developing anti...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12464
更新日期：2016-11-01 00:00:00
abstract：:BCL6 is a transcriptional repressor required in mature B cells during the germinal center (GC) reaction. Multiple mechanisms act coordinately to timely modulate BCL6 expression at transcriptional and post-transcriptional levels. BCL6 prevents premature activation and differentiation of GC B cells and provides an envir...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2012.01112.x
更新日期：2012-05-01 00:00:00
abstract：:5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) play a critical role in development and normal physiology. Alterations in 5-mC and 5-hmC patterns are common events in hematopoietic neoplasms. In this review, we begin by emphasizing the importance of 5-mC, 5-hmC, and their enzymatic modifiers in hematologic...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12242
更新日期：2015-01-01 00:00:00
abstract：:Inflammation underpins the development of atherosclerosis. Initiation and progression of vascular inflammation involves a complex cellular network, with macrophages as major contributors. Activated macrophages produce proinflammatory mediators, bridge innate and adaptive immunity, regulate lipid retention, and partici...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2007.00554.x
更新日期：2007-10-01 00:00:00
abstract：:Many tumors express antigens that can be specifically or selectively recognized by T lymphocytes, suggesting that T-cell-mediated immunity may be harnessed for the immunotherapy of cancer. However, since tumors originate from normal cells and evolve within the context of self-tissues, the immune mechanisms that preven...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12166
更新日期：2014-05-01 00:00:00
abstract：:One of the most toxic insults a cell can incur is a disruption of its linear DNA in the form of a double-strand break (DSB). Left unrepaired, or repaired improperly, these lesions can result in cell death or neoplastic transformation. Despite these dangers, lymphoid cells purposely introduce DSBs into their genome to ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2004.00165.x
更新日期：2004-08-01 00:00:00
abstract：:The actin cytoskeleton network forms a key link between T-cell antigen receptor (TCR) stimulation and T-cell effector functions, providing a structural basis for T-cell morphological changes and signal transduction. Accumulating evidence positions the Wiskott-Aldrich syndrome protein (WASp), a scaffolding protein that...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12112
更新日期：2013-11-01 00:00:00
abstract：:We first identified the RANTES chemokine as part of a search for genes expressed by T lymphocytes "late", 3-5 days, after T-cell activation. The kinetics of expression of RANTES and a small number of other genes are unusual and the mechanism of such delayed expression is unknown. In order to uncover a mechanism for su...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2000.17610.x
更新日期：2000-10-01 00:00:00
abstract：:Hematopoietic stem cell transplantation has been used for more than 50 years to combat hematologic malignancies. In addition to being the first stem cell therapy, transplantation has provided evidence for the potent anti-tumor effects of T cells. Facilitating T-cell-based immunity against malignancies requires a caref...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12142
更新日期：2014-01-01 00:00:00
abstract：:Viruses are obligatory intracellular parasites, whose replication depends on components encoded by the virus and pathways and functions of the host cell. In addition to the pathways required for viral synthesis, viruses activate multiple mechanisms to evade immune attack, promoting viral propagation while avoiding or ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2010.00909.x
更新日期：2010-05-01 00:00:00
abstract：:Pellinos are a family of E3 ubiquitin ligases discovered for their role in catalyzing K63-linked polyubiquitination of Pelle, an interleukin-1 (IL-1) receptor-associated kinase homolog in the Drosophila Toll pathway. Subsequent studies have revealed the central and non-redundant roles of mammalian Pellino-1, Pellino-2...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12298
更新日期：2015-07-01 00:00:00
abstract：:The characterization of the microenvironment of human tumors led to the description of tertiary lymphoid structures (TLS) characterized by mature dendritic cells in a T-cell zone adjacent to B-cell follicle including a germinal center. TLS represent sites of lymphoid neogenesis that develop in most solid cancers. Anal...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12405
更新日期：2016-05-01 00:00:00
abstract：:Regulatory T cells (Tregs) and the PD-1: PD-ligand (PD-L) pathway are both critical to terminating immune responses. Elimination of either can result in the breakdown of tolerance and the development of autoimmunity. The PD-1: PD-L pathway can thwart self-reactive T cells and protect against autoimmunity in many ways....
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2010.00923.x
更新日期：2010-07-01 00:00:00
abstract：:Adoptive transfer of TCR-transgenic T cells uniformly expressing an identifiable TCR of known peptide/MHC specificity can be used to monitor the in vivo behavior of antigen-specific T cells. We have used this system to show that naive T cells are initially activated within the T-cell zones of secondary lymphoid tissue...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1997.tb00959.x
更新日期：1997-04-01 00:00:00
abstract：:There are two distinct pathways by which T cells may recognize MHC alloantigens. The direct pathway involves T-cell recognition of intact MHC molecules expressed by donor antigen-presenting cells (APCs). The second, or indirect, pathway describes T-cell recognition of peptides derived from the processing and presentat...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01224.x
更新日期：1998-08-01 00:00:00
abstract：:Activation of immune cells to mediate an immune response is often triggered by potential 'danger' or 'stress' stimuli that the organism receives. Within the mitogen-activated protein kinases (MAPKs) family, the stress-activated protein kinase (SAPK) group was defined as group of kinases that activated by stimuli that ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2008.00744.x
更新日期：2009-03-01 00:00:00
abstract：:The monoclonal antibody, A2B4-2, specifically bound to and inhibited antigen-induced IL-2 release from the cloned pigeon cytochrome c-specific T cell hybrid, 2B4. The initial immunoprecipitation with these reagents demonstrated a protein of 85-90kd on non-reducing conditions, and two bands of 45-50 and 40-44 on reduci...
journal_title：Immunological reviews
pub_type： 杂志文章
doi：10.1111/j.1600-065x.1984.tb01107.x
更新日期：1984-10-01 00:00:00
abstract：:Hookworm infection is a major parasitic cause of morbidity in the developing nations of the tropics. Development of a genetically engineered vaccine would be a useful tool in the control of this infection in highly endemic areas. Recombinant polypeptides belonging to the Ancylostoma secreted protein (ASP)-1 family hav...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1999.tb01347.x
更新日期：1999-10-01 00:00:00
abstract：:TET proteins are DNA demethylases that can oxidize 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC) and other oxidized mC bases (oxi-mCs). Importantly, TET proteins govern cell fate decisions during development of various cell types by activating a cell-specific gene expression program. In this review...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12940
更新日期：2021-01-07 00:00:00
abstract：:In the last decade, the paradigm of primary immunodeficiencies (PIDs) as rare recessive familial diseases that lead to broad, severe, and early-onset immunological defects has shifted toward collectively more common, but sporadic autosomal dominantly inherited isolated defects in the immune response. Patients with PID...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12898
更新日期：2020-09-01 00:00:00
abstract：:GITR [glucocorticoid inducible tumor necrosis factor receptor (TNFR)-related protein] and 4-1BB are costimulatory TNFR family members that are expressed on regulatory and effector T cells as well as on other cells of the immune system. Here we discuss the role of GITR and 4-1BB on T cells during viral infections and i...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2011.01063.x
更新日期：2011-11-01 00:00:00
abstract：:Interest in DNA immunization of animals continues, despite the fact that immune responses induced by DNA vaccines are generally lower than those elicited by conventional vaccines. In attempts to enhance the immune response to DNA vaccines, individuals have tried a variety of immune modulators, cytokines, and costimula...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2004.00140.x
更新日期：2004-06-01 00:00:00
