Abstract：
:We review a novel strategy for tolerance induction developed in rhesus macaques and termed STEALTH. We summarize the evolution of the STEALTH model, the results of successful trials in inducing long-term, stable transplant tolerance in rhesus kidney and diabetic islet recipients and discuss information related to the mechanism by which durable tolerance is induced. STEALTH tolerance is induced by a 3-day treatment course of CD3epsilon immunotoxin (IT) combined with a 14-day treatment with deoxyspergualin (DSG). IT causes profound depletion of sessile lymph node T cells as well as the more accessible circulating T cells. DSG, an inhibitor of HSC 70-mediated NF-kappaB nuclear translocation, arrests maturation of myeloid dendritic cells, blocks production of proinflammatory cytokines induced by IT administration, and promotes systemic production of Th2 type cytokines that persist indefinitely. Such Th2 cytokine deviation has not been reported in NHP transplant recipients. These studies provide proof of principle in a preclinical model that prevention of both acute and chronic allograft rejection, for at least 2.2-4.9 years of follow-up, can be achieved in NHP in the absence of chronic immunosuppressive drugs or other interventions. This strategy for inducing NHP tolerance is discussed in relation to current tolerance paradigms.
journal_name
Immunol Revjournal_title
Immunological reviewsauthors
Thomas JM,Hubbard WJ,Sooudi SK,Thomas FTdoi
10.1034/j.1600-065x.2001.1830118.xkeywords:
subject
Has Abstractpub_date
2001-10-01 00:00:00pages
223-33eissn
0105-2896issn
1600-065Xpii
1830118journal_volume
183pub_type
杂志文章,收录出版,评审abstract：:In the quest for effective immunization against complex diseases such as cancer, parasitic diseases, AIDS, and other viral infections, numerous peptides and recombinant proteins have been synthesized, examined for the ability to induce antibodies and CTLs, and tested for binding capability and therapeutic or prophylac...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1995.tb00075.x
更新日期：1995-06-01 00:00:00
abstract：:Determination of the crystal structure of class II: peptide complexes has shown that in addition to pocket interactions involving the side chains of the peptide, peptide binding to MHC class II molecules is characterized by a series of hydrogen bonds which are contributed by genetically conserved amino acid residues i...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1999.tb01369.x
更新日期：1999-12-01 00:00:00
abstract：:The structure and amino acid diversity of the T-cell receptor (TCR), similar in nature to that of Fab portions of antibodies, would suggest that these proteins have a nearly infinite capacity to recognize antigen. Yet all currently defined native T cells expressing an α and β chain in their TCR can only sense antigen ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12327
更新日期：2015-09-01 00:00:00
abstract：:We have discussed some aspects of the structure of the normal immune system, particularly the B-cell compartment. We have argued: that a basic property of the natural antibody repertoire is constituted by high degrees of connectivity within the immune system as well as between the system and other components of the or...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1989.tb00028.x
更新日期：1989-08-01 00:00:00
abstract：:The substantial importance of P-selectin glycoprotein ligand 1 (PSGL-1) in leukocyte trafficking has continued to emerge beyond its initial identification as a selectin ligand. PSGL-1 seemed to be a relatively simple molecule with an extracellular mucin domain extended as a flexible rod, teleologically consistent with...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2009.00797.x
更新日期：2009-07-01 00:00:00
abstract：:Regulatory T cells (Tregs) are critical to the human immune system, providing appropriately scaled immune responses and mediating peripheral tolerance. A central role for forkhead box protein 3 (FoxP3)(+) Tregs has been shown in the pathogenesis of mechanistically diverse central nervous system (CNS) diseases from aut...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2012.01130.x
更新日期：2012-07-01 00:00:00
abstract：:We have discussed four specific models which provide different kinds of information about the requirements for T cell activation. The first utilized a CTL clone designated L3, which is reactive specifically with Ld alloantigen, to study the involvement of the associative recognition structure Lyt-2 in cytolysis. The a...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1984.tb01105.x
更新日期：1984-10-01 00:00:00
abstract：:In this review, we discuss the possibilities for combining the power of molecular analysis of the antigens expressed in a given individual tumor with the design of a tailored vaccine containing defined antigens. Step 1 is a differential gene expression analysis of tumor and corresponding normal tissue. Step 2 is the a...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2002.18815.x
更新日期：2002-10-01 00:00:00
abstract：:The discovery of antibodies specific for citrullinated protein epitopes [anti-citrullinated protein antibodies (ACPAs)] is a hallmark for the diagnosis and prognosis of rheumatoid arthritis (RA) and will also be a useful tool for understanding the fundamental pathologic processes. There are several essential questions...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2009.00853.x
更新日期：2010-01-01 00:00:00
abstract：:Cancers are able to grow by subverting immune suppressive pathways, to prevent the malignant cells as being recognized as dangerous or foreign. This mechanism prevents the cancer from being eliminated by the immune system and allows disease to progress from a very early stage to a lethal state. Immunotherapies are new...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12528
更新日期：2017-03-01 00:00:00
abstract：:Francisella tularensis in an intracellular bacterial pathogen that causes a potentially lethal disease called tularemia. Studies performed nearly 100 years ago revealed that neutrophil accumulation in infected tissues correlates directly with the extent of necrotic damage during F. tularensis infection. However, the d...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12445
更新日期：2016-09-01 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：:In mice, the absence of terminal deoxynucleotidyl transferase (Tdt) expression during fetal and neonatal life provides a window in development where clones of lymphocytes are generated that provide protective immunity. Introducing premature Tdt activity interferes with the development of these clones and results in an...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：
更新日期：2000-06-01 00:00:00
abstract：:The nuclear factor-κB (NF-κB) pathway is a critical regulator of innate and adaptive immunity. Noncanonical K63-linked polyubiquitination plays a key regulatory role in NF-κB signaling pathways by functioning as a scaffold to recruit kinase complexes containing ubiquitin-binding domains. Ubiquitination is balanced by ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2012.01100.x
更新日期：2012-03-01 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：:Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by immune-mediated destruction of the biliary epithelial cells (BEC) lining the intrahepatic bile ducts (non-suppurative destructive cholangitis (NSDC)). Autoantibody and autoreactive T-cell responses specific for the self-antigen pyruvate de...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-0528.2002.00021h.x
更新日期：2000-04-01 00:00:00
abstract：:Solid organ transplantation is a vital therapy for end stage diseases. Decades of research have established that components of the adaptive immune system are critical for transplant rejection, but the role of the innate immune system in organ transplantation is just emerging. Accumulating evidence indicates that the i...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12146
更新日期：2014-03-01 00:00:00
abstract：:Nuclear-factor κB (NF-κB) transcription factors are activated by a wide variety of stimuli in diverse cell types and control key aspects of immune function and development. Receptor-mediated activation of NF-κB appears to occur through two distinct signaling pathways termed as the canonical and non-canonical NF-κB pat...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2011.01059.x
更新日期：2011-11-01 00:00:00
abstract：:Hepatitis is damage and inflammation of the liver. It is triggered by both environmental and endogenous insults and is a platform for developing liver cirrhosis and cancer. Both innate and adaptive immune activation contribute to hepatic inflammation and disease. Viral hepatitis is the most common form of hepatitis an...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12279
更新日期：2015-05-01 00:00:00
abstract：:Studies of the regulation of gene expression historically focused on transcription. However, during stress and apoptosis, profound gene expression changes occur more rapidly and globally than is possible by regulating transcription. Posttranscriptional changes in mRNA processing and translation in response to diverse ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12052
更新日期：2013-05-01 00:00:00
abstract：:The infiltration of human tumors by T cells is a common phenomenon, and over the past decades, it has become increasingly clear that the nature of such intratumoral T-cell populations can predict disease course. Furthermore, intratumoral T cells have been utilized therapeutically in clinical studies of adoptive T-cell...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12140
更新日期：2014-01-01 00:00:00
abstract：:Cancer immunotherapy utilizing T-cell checkpoint inhibitors has shown tremendous clinical success. Yet, this mode of treatment is effective in only a subset of patients. Unresponsive patients tend to have non-T-cell-inflamed tumors that lack markers associated with the activation of adaptive anti-tumor immune response...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12522
更新日期：2017-03-01 00:00:00
abstract：:Peptides derived from parasites are presented to T helper cells by major histocompatibility complex (MHC) class II alpha beta heterodimeric cell-surface molecules. In mice and humans, the genes encoding these antigen-presenting molecules are known to be polymorphic and polygenic. Multiple loci for MHC class II A and B...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01270.x
更新日期：1998-12-01 00:00:00
abstract：:The preceding paragraphs describe several uses of specific antibodies to IL-1. Standard radioimmunoassays and ELISA procedures were developed with demonstrated utility in studies attempting to quantitate the cytokine in cell culture fluids. In part, antibody-based assays circumvent the problems associated with bioassa...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1991.tb00584.x
更新日期：1991-02-01 00:00:00
abstract：:IgG dimers occurring in therapeutic Ig preparations have been characterized as Id-anti-Id, in that the sites of interaction are localized to the distal tips of the Fab arms. The observation that such dimers are prevalent in Ig or Igi.v. prepared from large plasma pools, but absent in preparations from a single individ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1994.tb00861.x
更新日期：1994-06-01 00:00:00
abstract：:The ability to engineer the antibody molecule has now progressed to the stage where one can realistically contemplate creating a pharmacologically useful targeting molecule comprising a single-chain, minimal antibody combining site together with a domain that imparts a second functionality. It will certainly be possib...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1992.tb01526.x
更新日期：1992-12-01 00:00:00
abstract：SUMMARY:Dengue viruses (DENV) are the mosquito-borne viruses of greatest global public health importance. DENV circulate as four serotypes with significant immunologic cross-reactivity that does not provide protection from secondary infection with heterologous serotypes. The strong association of severe dengue illness,...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2008.00678.x
更新日期：2008-10-01 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：:T cells are key players of the mammalian adaptive immune system. They experience different mechanical microenvironments during their life cycle, from the thymus, secondary lymph organs, and peripheral tissues that are free of externally applied force, but display variable substrate rigidities to the blood and lymphati...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12122
更新日期：2013-11-01 00:00:00
abstract：:Studies in the last 20 years have given us a remarkable insight into the functional and phenotypic diversity of macrophages which reflects their integral role in host defence, homeostasis and pathogenesis. Mouse genetics, transcriptomic and epigenetic studies have provided an ontogenic and molecular perspective to the...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12603
更新日期：2017-11-01 00:00:00
