Clinical and applied immunology reviews最新文献

{"title":"Problems and solutions to successful gene-transfer based therapies for HIV","authors":"John A. Zaia M.D.","doi":"10.1016/S1529-1049(02)00157-5","DOIUrl":"10.1016/S1529-1049(02)00157-5","url":null,"abstract":"<div><p>Since the late 1980s, when the potential for intracellular immunization using genetic methods was first suggested <span>[1]</span>, there has been a dream that someday gene transfer methods might be available for treatment of human immunodeficiency virus (HIV)-1 infection. The goals of such gene transfer would be control of HIV-1 infection without the need for chemotherapy and the protection of the immune system from further infection with HIV-1. Thus, at the minimum, it would be expected that any functional genes expressed for this purpose would have antiviral effects sufficient to control infection and able to be expressed in T lymphocytes and macrophages targeted by HIV-1.</p><p><span><span><span><span>The pathogenesis of acquired immunodeficiency syndrome (AIDS), however, is an ongoing process in which HIV-1 infection initially alters the various </span>tissues of the immune system, including not only T lymphocytes but also the </span>thymus, in which T cell maturation occurs. In addition, the lymph nodes and dendritic cells, which are important for immune protection, and the bone marrow, which is essential for continued immune cell propagation are altered by </span>HIV infection. Virus progression is undoubtedly a dynamic process, and any eventual gene therapy of HIV-1 infection that seeks to use these tissues must consider the effect that HIV has during the various periods of this progression. During a period that usually takes several years, the virus infection has a selective influence on the lymphoid compartment, reduces the available numbers of T lymphocytes, and alters their function </span><span>2</span>, <span>3</span>, <span>4</span>, <span>5</span>, <span>6</span><span><span>. The next period of pathogenesis begins with the initiation of potent anti-retroviral therapy (ART), in which there is a selective expansion of T cells during the beginning of immune reconstitution. Here, there is an antigen-driven disproportionate stimulation of CD8 and CD4 cells that leads to an aberrant immune reconstitution due to oligoclonal expansion of cells reactive to the antigens present at the time, usually HIV-1, </span>cytomegalovirus (CMV), and Epstein-Barr virus (EBV) </span><span>[7]</span><span>. Finally, there is a gradual restoration of the immune repertoire<span> toward normalcy. It is recognized that this reconstitution varies in different persons based on residual thymic function, duration of untreated HIV-1 infection, age, and other factors, and it is not clear if this ever returns to normalcy. Thus, the lymphoid populations in most need of protection from HIV-1 often have a skewed functional capacity. In the case of stem cell gene therapy approaches, the target cells depend on a site, the marrow, which may have altered or limited supportive capacity. The issues add to the problems that must be faced in bringing gene therapy approaches to the clinic.</span></span></p></div>","PeriodicalId":89340,"journal":{"name":"Clinical and applied immunology reviews","volume":"3 4","pages":"Pages 199-211"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1529-1049(02)00157-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56629629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dr. Nava Sarver","authors":"Sandra Bridges Ph.D.,&nbsp;Cairns Ph.D.,&nbsp;Susan Plaeger Ph.D.,&nbsp;Nabila Wassef Ph.D.,&nbsp;Janet Young Ph.D.","doi":"10.1016/S1529-1049(02)00162-9","DOIUrl":"10.1016/S1529-1049(02)00162-9","url":null,"abstract":"","PeriodicalId":89340,"journal":{"name":"Clinical and applied immunology reviews","volume":"3 4","pages":"Page 153"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1529-1049(02)00162-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56629602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering DNA vaccination as an approach to HIV immune therapy","authors":"Jean D. Boyer ,&nbsp;Michele A. Kutzler ,&nbsp;Michael A. Chattergoon ,&nbsp;Sandra A. Calarota ,&nbsp;George Pavlakis ,&nbsp;Rafick-Pierre Sekaly ,&nbsp;Rob Roy MacGregor ,&nbsp;David B. Weiner","doi":"10.1016/S1529-1049(02)00158-7","DOIUrl":"10.1016/S1529-1049(02)00158-7","url":null,"abstract":"<div><p><span><span>Deoxyribonucleic acid (DNA) vaccination, also known as genetic immunization, is a novel vaccine technology that has been tested in humans for many current infectious diseases, and has been found to be well-tolerated. The approach has been used to induce protective immunity against infectious pathogens, malignancies, as well as prevent the development of autoimmune disorders in animal models. Moreover, DNA vaccines have been tested for clinical use as both prophylactic and therapeutic agents. For these vaccines, </span>plasmid DNA<span> encoding a polypeptide/protein antigen is introduced into a host where it enters host cells and serves as an epigenetic<span> template for the high efficiency translation of antigen. Although DNA immunogens have been shown to stimulate both the cellular and/or humoral arms of the immune system, improving the potency of these vaccines is clearly important. In this regard, several approaches to improve efficacy are currently being tested and will be discussed in this review. One such approach is to improve the DNA plasmid by introducing codon optimization in the DNA plasmid that improves expression and immunogenicity<span> in animals. A second approach aims to manipulate the host immune response by including immunologic molecular adjuvants as part of the vaccine including T cell costimulatory molecules, cytokines, and </span></span></span></span>chemokines<span><span>. Using immunologic adjuvants, researchers have tailored the immune response to the DNA vaccine toward a particular Th subtype, allowing for the preferential induction of predominantly cell-mediated or </span>humoral response<span>. In particular, interleukin-15 (IL-15) expands CD8 immune responses in the absence of T cell help, while chemokines attract dendritic cells as well as other professional antigen presenting cells, directly activating T and/or B cells in the periphery. Furthermore, priming with such adjuvanted DNAs and boosting with T cell costimulatory molecules further enhances antigen-specific immune response to the DNA antigen. Combining these approaches may be particularly useful against human immunodeficiency virus (HIV) infection, in which both cell-mediated and humoral immune responses are required to fight infection. Ultimately, clinical evidence of these approaches may influence not just how we approach HIV treatment, but also treatments for other infectious diseases, autoimmunity, and cancer.</span></span></p></div>","PeriodicalId":89340,"journal":{"name":"Clinical and applied immunology reviews","volume":"3 4","pages":"Pages 183-197"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1529-1049(02)00158-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56629765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using new gene delivery systems to advance HIV gene therapy","authors":"David S. Strayer ,&nbsp;Harris Goldstein ,&nbsp;Pierre Cordelier ,&nbsp;Siddhartha Ghosh ,&nbsp;Marlene S. Strayer ,&nbsp;Massimo Pettoello-Mantovani ,&nbsp;J.Roy Chowdhury","doi":"10.1016/S1529-1049(03)00008-4","DOIUrl":"10.1016/S1529-1049(03)00008-4","url":null,"abstract":"<div><p><span>Progress in gene therapy of human immunodeficiency virus (HIV) infection from laboratory to bedside, as for gene therapy in general, has been slow. Many transgenes, some very innovative, have been shown to inhibit HIV in cultured cells. But translation of such results to humans, or even to animal models of acquired immunodeficiency syndrome (AIDS), has been problematic. Among the reasons for this failure is ineffective gene delivery. Most </span>gene delivery systems<span> used for this purpose are limited by low production titers, fragility, poor transduction efficiency, waning transgene expression over time, requirements for ex vivo<span> manipulation of target cells that constrain key aspects of these cells' utility on reimplantation, etc. These restrictions both prevent successful anti-HIV gene therapy and limit the scope of ideas as to how anti-HIV gene therapy may be used.</span></span></p><p><span>Application of recombinant gene delivery vectors derived from simian virus-40 (rSV40s) may help to address many of these problems:</span></p><ul><li><span>1.</span><span><p><span>They transduce all HIV-susceptible cell types (lymphocytes, monocytes<span>, dendritic cells, neurons, microglia, etc.) and their progenitors (e.g., CD34+ cells) with &gt;95% efficiency without selection, whether as </span></span>cell lines or as primary cells, resting or dividing;</p></span></li><li><span>2.</span><span><p>Transgenes targeting almost every phase of the HIV-1 replicative cycle, from cell entry to virion morphogenesis have been delivered using these vectors. Individual transgenes vary in their abilities to inhibit HIV, but all do so.</p></span></li><li><span>3.</span><span><p>Strains of HIV-1 inhibited by rSV40 gene delivery include laboratory and clinical isolates, X4-, R5- and dual-tropic viruses, and neurotropic strains (including CD4-independent HIV-1).</p></span></li><li><span>4.</span><span><p>High transduction efficiency allows sequential transduction with multiple different rSV40s. Nearly all unselected cells treated with two different rSV40s are transduced by both. Combinations of transgenes provide far greater protection than any transgene individually.</p></span></li><li><span>5.</span><span><p>Vector deoxyribonucleic acids (DNAs) integrate rapidly into the cellular DNA, assuring permanent transduction. Transgene expression has not diminished with time.</p></span></li><li><span>6.</span><span><p>When severe combined immunodeficiency<span> (SCID)-hu mice carrying implanted human tissues were transduced with a rSV40 vector in vivo, and then challenged with HIV in vivo, it provided the first demonstration that in vivo gene transfer with rSV40 vectors can inhibit HIV in vivo.</span></p></span></li><li><span>7.</span><span><p>These vectors are safe.</p></span></li></ul><p>Although this gene delivery system has limitations (transgenes must be smaller than 5 kb; some common nonvertebrate marker genes like green fluorescent protein are no","PeriodicalId":89340,"journal":{"name":"Clinical and applied immunology reviews","volume":"3 4","pages":"Pages 247-259"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1529-1049(03)00008-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56630318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gamma/delta T cells","authors":"Miroslav Malkovsky ,&nbsp;Paul Fisch ,&nbsp;Marianne Wallace ,&nbsp;Aparna Sen ,&nbsp;Gloria Mejia ,&nbsp;Mark G. Lewis ,&nbsp;Julianna Lisziewicz ,&nbsp;Franco Lori ,&nbsp;Fabrizio Poccia","doi":"10.1016/S1529-1049(02)00154-X","DOIUrl":"https://doi.org/10.1016/S1529-1049(02)00154-X","url":null,"abstract":"<div><p><span>Protection from exogenous invaders and elimination of endogenous aberrations are the main contributions of T cells to homeostasis<span>. T cells with Vγ9Vδ2-encoded T-cell receptors (TCRs) have a unique ability to interact with a plethora of phosphoantigens in a major histocompatibility complex<span><span><span> (MHC)-unrestricted manner. The biological function of this recognition is largely unclear. However, since Vγ9Vδ2 T cells are potent cytotoxic effectors capable of killing tumor cells and target cells infected with numerous viruses including human immunodeficiency virus (HIV), simian immunodeficiency virus (SIV), </span>herpes viruses and many others, it is likely that they are involved in antitumor and antiviral </span>immunosurveillance. The observations of tumor-infiltrating γδ T cells with cytotoxic properties and profound quantitative and functional changes in γδ T cells associated with various infectious diseases (including those caused by viruses) are compatible with this hypothesis. For example, the most frequent human peripheral blood γδ T-cell subset expressing Vγ9Vδ2 TCRs is functionally disabled and numerically decreased in some HIV-infected persons. The nonresponsiveness of Vγ9Vδ2 T cells is accompanied by their decreased IFNγ and TNFα production. The overall level of γδ T-cell activation at different stages of </span></span></span>HIV infection<span> may be clinically relevant. At an initial stage of HIV infection, the extremely potent antiviral cytotoxic activities of Vγ9Vδ2 T cells may limit the viral spread. At later stages of disease, Vγ9Vδ2 T-cell dysfunction may contribute to the loss of resistance to opportunistic pathogens (such as atypical mycobacteria) and neoplasms (e.g., lymphomas) frequently associated with HIV infections. The activity of Vγ9Vδ2 T cells both in vivo and can be regulated by nonpeptidic antigens. These molecules are being assessed as potential therapeutic vaccines in acquired immunodeficiency syndrome (AIDS) and certain cancers susceptible to the Vγ9Vδ2 T-cell attack.</span></p></div>","PeriodicalId":89340,"journal":{"name":"Clinical and applied immunology reviews","volume":"3 4","pages":"Pages 235-245"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1529-1049(02)00154-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137158610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Applied Immunology Reviews","authors":"","doi":"10.1016/S1529-1049(03)00025-4","DOIUrl":"10.1016/S1529-1049(03)00025-4","url":null,"abstract":"","PeriodicalId":89340,"journal":{"name":"Clinical and applied immunology reviews","volume":"3 4","pages":"Page IFC"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1529-1049(03)00025-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"98598077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-mitochondrial autoantibodies","authors":"Marvin J Fritzler ,&nbsp;Michael P Manns","doi":"10.1016/S1529-1049(02)00058-2","DOIUrl":"10.1016/S1529-1049(02)00058-2","url":null,"abstract":"<div><p><span>Anti-mitochondrial antibodies (AMA) are a serological hallmark of primary biliary cirrhosis<span> (PBC). The major autoantibody targets are located in the inner mitochondrial membrane<span>, are encoded by nuclear genes and are components of the 2-oxo acid dehydrogenase complexes. Greater than 90% of PBC patients react with one or more of these </span></span></span>autoantigens<span><span><span>. The major epitopes have been mapped to the lipoic acid binding domain. The apparent hepatic targets of immune destruction, the apical biliary epithelial cells, express proteins that mimic these epitopes. Nevertheless, the role of AMA in biliary pathology is not clear and observed abnormalities may be due to T-cells that respond to similar epitopes. AMAs are often accompanied by autoantibodies to other intracellular components such as the </span>nuclear pore complex, centromeres/kinetochores, and other </span>nuclear antigens. The origin or inciting agent(s) of AMA is not known but epidemiological and immunological evidence implicates environmental agents.</span></p></div>","PeriodicalId":89340,"journal":{"name":"Clinical and applied immunology reviews","volume":"3 3","pages":"Pages 87-113"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1529-1049(02)00058-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56628179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measuring and evaluating the significance of autoantibodies in neurological disorders","authors":"Angela Vincent MB, BS, FRCPath","doi":"10.1016/S1529-1049(02)00081-8","DOIUrl":"10.1016/S1529-1049(02)00081-8","url":null,"abstract":"<div><p>There is increasing use of antibody measurements for diagnosing well-established autoimmune disorders of the nervous system, and in the investigation of other less well characterized diseases. Antibodies against muscle or neuronal ion channels, and against myelin<span> glycolipids<span> are clearly associated with peripheral neurological diseases. Some of these antibodies are also being identified in central nervous system (CNS) disorders, where their pathogenic role has yet to be clearly demonstrated. Antibodies to intracellular antigens, that are co-expressed by certain tumors, are found in patients with paraneoplastic neurological disorders and are very important as tumor markers, but the conditions are probably the result of a T-cell mediated attack. This review will discuss the methods currently in use for measuring these antibodies, their importance in clinical practice, and indicate new developments.</span></span></p></div>","PeriodicalId":89340,"journal":{"name":"Clinical and applied immunology reviews","volume":"3 3","pages":"Pages 127-151"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1529-1049(02)00081-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56629267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoregulation by probiotic lactobacilli","authors":"Martin L Cross","doi":"10.1016/S1529-1049(02)00057-0","DOIUrl":"10.1016/S1529-1049(02)00057-0","url":null,"abstract":"<div><p><span><span>Probiotic<span> lactobacilli are able to transiently survive in the human gastrointestinal tract following oral delivery, where they may signal </span></span>sentinel cells<span><span> of the immune system (such as those expressing pattern recognition receptors). Recent evidence suggests that the form of immune signal is strongly strain-dependent, with some well-defined bacterial strains potentiating systemic T helper (Th) 1-type immune activity and favoring cell-mediated immunity (CMI). Clinical studies have shown promising outlets for the use of non-pathogenic lactobacilli as provisioners of pro-Th1 immune signals in anti-allergy and anti-tumor </span>immunotherapy, as well as combating intracellular microbial infections and </span></span>immunosenescence. The underlying process appears to involve pro-Th1 activating cytokines (IFNα/IFNγ, IL-12, and IL-18) generated following bacterial contact with accessory leukocytes. The utilization of pro-Th1/CMI lactobacilli in present and future clinical immunotherapy is discussed.</p></div>","PeriodicalId":89340,"journal":{"name":"Clinical and applied immunology reviews","volume":"3 3","pages":"Pages 115-125"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1529-1049(02)00057-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56628147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum free light chain immunoassays and their clinical application","authors":"A.R. Bradwell FRCP ,&nbsp;H.D.Carr-Smith Ph.D ,&nbsp;G.P.Mead Ph.D ,&nbsp;M.T. Drayson","doi":"10.1016/S1529-1049(02)00064-8","DOIUrl":"10.1016/S1529-1049(02)00064-8","url":null,"abstract":"<div><p><span>Measurement of urine free light chains (flc) is important for assessing monoclonal plasma cell diseases. However, since the kidneys metabolize large amounts of flc, urine concentrations may not accurately reflect plasma cell synthesis. From a theoretical viewpoint, serum measurements would be preferable, just as </span>blood glucose<span><span> measurements are preferable to urine measurements for managing patients with diabetes mellitus. Unfortunately, the development of satisfactory serum flc immunoassays has been hampered by the lack of specific, high-affinity antisera. Recent publications indicate that this situation has now changed. Serum flc have been quantified using routine clinical laboratory instruments and have produced useful diagnostic results in several diseases. Thus, 100% of patients with light-chain multiple </span>myeloma<span>, 75% of patients with nonsecretory myeloma and more than 95% of patients with primary amyloidosis could be diagnosed using serum flc assays. This improvement in disease detection rates and the potential for superior disease monitoring may obviate the need for urine flc tests in most patients with monoclonal plasma cell diseases.</span></span></p></div>","PeriodicalId":89340,"journal":{"name":"Clinical and applied immunology reviews","volume":"3 1","pages":"Pages 17-33"},"PeriodicalIF":0.0,"publicationDate":"2002-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1529-1049(02)00064-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56628440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}