Abstract:
:Programmed cell death-1 (PD-1, Pdcd1), an immunoreceptor belonging to the CD28/CTLA-4 family negatively regulates antigen receptor signaling by recruiting protein tyrosine phosphatase, SHP-2 upon interacting with either of two ligands, PD-L1 or PD-L2. Because of the wide range of ligand distribution in the body, its biological significance pervades almost every aspect of immune responses including autoimmunity, tumor immunity, infectious immunity, transplantation immunity, allergy and immunological privilege. In this review, we would like to summarize the history of PD-1 research since its discovery and recent findings that suggest promising future for the clinical application of PD-1 agonists and antagonists to various human diseases.
journal_name
Int Immunoljournal_title
International immunologyauthors
Okazaki T,Honjo Tdoi
10.1093/intimm/dxm057subject
Has Abstractpub_date
2007-07-01 00:00:00pages
813-24issue
7eissn
0953-8178issn
1460-2377pii
dxm057journal_volume
19pub_type
杂志文章,评审abstract::The mature dendritic cell (DC) is considered to be the most potent antigen-presenting cell. Regulation of the DC, particularly its survival, is therefore critical. Mature DC are markedly more sensitive to HLA-DR-mediated apoptosis than immature DC. To further characterize this key survival difference, we compared the ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxf058
更新日期:2002-08-01 00:00:00
abstract::The role of adjuvant on the T(h)1 and T(h)2 immune responses to Abeta-immunotherapy (Abeta(42 )peptide) was examined in wild-type mice. Fine epitope analysis with overlapping oligomers of the Abeta(42) sequence identified the 1-15 region as a dominant B cell epitope. The 6-20 peptide was recognized only weakly by anti...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg049
更新日期:2003-04-01 00:00:00
abstract::The intestinal epithelium not only acts as the physical structure that separates the intestinal lumen from the body but also actively participates in intestinal barrier functions. In the past decade, significant progress has been made in the development of culture technologies to maintain intestinal epithelial cells (...
journal_title:International immunology
pub_type: 杂志文章,评审
doi:10.1093/intimm/dxy065
更新日期:2019-02-06 00:00:00
abstract::T cell responses against complex antigens are often directed against a limited set of immunodominant determinants. We have studied this phenomenon at the level of cellularly processed peptides recognized by CTL in the B6 anti-BALB.B minor histocompatibility (H) barrier, comprising at least 29 antigen loci. B6 anti-BAL...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.6.919
更新日期:1995-06-01 00:00:00
abstract::The A6H mAb raised primarily against human renal cell carcinoma (RCC) has previously been shown to bind strongly to RCC, to some degree to colon carcinoma but only marginally to a variety of normal tissues. Immunohistochemical analysis or RCC tissues containing tumor-infiltrating lymphocytes revealed that A6H stained ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.9.1425
更新日期:1995-09-01 00:00:00
abstract::Signal transducer and activator of transcription-1 (STAT1) signaling mediate most biological functions of IFNalpha, IFNbeta and IFNgamma although recent studies indicate that IFNgamma can alter expression of several genes via a STAT1-independent pathway. STAT1 is critical for immunity against a variety of intracellula...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn119
更新日期:2009-01-01 00:00:00
abstract::To investigate potential roles of the RAG-1 and RAG-2 gene products in Ig heavy chain class recombination (CSR), we have generated RAG-1(-/-) and RAG-2(-/-) mice which contain both a rearranged Ig HC V(D)J gene (referred to as B1-8) inserted into the endogenous Ig heavy chain (HC) locus in place of the JH segments, an...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.3.325
更新日期:1998-03-01 00:00:00
abstract::Antigen engagement of the TCR may lead to activation of mature T cells while inducing deletion or positive selection of immature thymocytes. Using thymocytes from TCR transgenic mice recognizing the allo-antigen H-2Kb we investigated whether double-positive CD4+CD8+ (DP) thymocytes constitute a particular developmenta...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.9.1421
更新日期:1996-09-01 00:00:00
abstract::Dendritic cells (DC) sense saprophytic yeast and pathogenic, filamentous forms of Candida albicans in a specific way, resulting in disparate patterns of DC and T(h) cell activation. Using human and murine DC, such disparate patterns could be traced to the exploitation of distinct recognition receptors. Although usage ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh012
更新日期:2004-01-01 00:00:00
abstract::Mutagenic analyses have identified structural motifs important for TCR-mediated signaling in the antigen-binding chains, CD3 and zeta subunits of the TCR complex. In this study, we altered selected residues in the transmembrane and extracellular constant regions of the TCR beta chain and expressed the mutants in a T h...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.7.923
更新日期:1998-07-01 00:00:00
abstract::The non-obese diabetic (NOD) mouse spontaneously develops T-cell-mediated autoimmune insulitis. We analyzed the clonotypes of T cell infiltrates of the NOD mouse islets using a new method we have developed recently, which consists of RT-PCR amplification of the CDR3 region of the TCR beta chain mRNA and subsequent sin...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.6.807
更新日期:1996-06-01 00:00:00
abstract::In humans, the thymus is the primary lymphoid organ able to support the development of T cells through its three-dimensional (3D) organization of the thymic stromal cells. Since a remarkable number of similarities are shared between the thymic epithelial cells (TECs) and skin-derived keratinocytes and fibroblasts, in ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxt035
更新日期:2013-12-01 00:00:00
abstract::Under equilibrium conditions, the affinities of five anti-IgG2a mAb isolated from virus-infected mice were comparable to other high-affinity auto-antibodies. Similar to rheumatoid factors, these anti-IgG2a auto-antibodies bound to aggregated or complexed IgG2a with 50 to 1500-fold higher avidity than their monomeric c...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.7.1125
更新日期:1995-07-01 00:00:00
abstract::We established an experimental system in vitro to examine the developmental capacity of individual hematopoietic progenitors to generate T, B and myeloid (M) cells. By using this system we analyzed the process of lineage commitment of hematopoietic progenitors in murine fetal liver (FL). It is known that small numbers...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.7.1011
更新日期:1997-07-01 00:00:00
abstract::A canonical pre-TCR/TCR signaling pathway critical for thymic T cell development involves sequential phosphorylation and signaling through Lck, Zap70, Lat and Slp76. However, we and others have previously reported that genomic deletion of c-Cbl (Cbl) partially or completely reverses the defects in thymic development i...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxu105
更新日期:2015-05-01 00:00:00
abstract::IFN-regulatory factor (IRF)-4 is a member of the IRF family of transcription factors expressed in lymphocytes and macrophages. The previous studies using mice deficient in the IRF-4 gene showed profound defects in function of both B and T cells. To further investigate the role of IRF-4 in CD4(+) T cell function, IRF-4...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg001
更新日期:2003-01-01 00:00:00
abstract::To investigate the role of the Toll-like receptor (TLR) family in host defense against Toxoplasma gondii, we infected TLR2-, TLR4- and MyD88-deficient mice with the avirulent cyst-forming Fukaya strain of T. gondii. All TLR2- and MyD88-deficient mice died within 8 days, whereas all TLR4-deficient and wild-type mice su...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg108
更新日期:2003-09-01 00:00:00
abstract::Sphingosine 1-phosphate (S1P) and S1P receptor 1 (S1P1) play an important role in the egress of mature CD4 or CD8 single-positive (SP) thymocytes from the thymus. Fingolimod hydrochloride (FTY720), an S1P1 functional antagonist, induced significant accumulation of CD62L(high)CD69(low) mature SP thymocytes in the thymi...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxt069
更新日期:2014-05-01 00:00:00
abstract::Several cytokines and chemokines including chemokine (C-C motif) ligand-2 (CCL2) are induced in HIV-1 infection. However, the impact of HIV-1 viremia on CCL2 regulation is largely unknown. We utilized a DNA oligonucleotide microarray covering 110 inflammatory genes. Five genes were induced by at least 2-fold in PBMCs ...
journal_title:International immunology
pub_type: 临床试验,杂志文章
doi:10.1093/intimm/dxl078
更新日期:2006-10-01 00:00:00
abstract::Responsiveness of dendritic cells (DC) to inflammatory CC chemokines is down-regulated during their maturation. We analyzed the mechanism underlying these events. Cell-surface expression of CC chemokine receptor (CCR)-1, -3 and -5 was increased during differentiation of immature DC (iDC) from monocytes. In contrast, t...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/13.2.167
更新日期:2001-02-01 00:00:00
abstract::Murine bone marrow-derived macrophages (BMM) are able to inhibit the intracellular growth of Mycobacterium bovis and Mycobacterium tuberculosis H37Rv after activation with recombinant (r) IFN and growth inhibition is mediated by reactive nitrogen intermediates (RNI) derived from L-arginine. We now demonstrate that tum...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.5.693
更新日期:1994-05-01 00:00:00
abstract::Based on the similarity in primary structure between the newly characterized ligand for CD40 (CD40L) and the tumor necrosis factors (TNFs), we have modeled a detailed 3-D structure for CD40L. We used the known structure of TNF alpha as a template for the generation of the CD40L model. The soundness of the model-buildi...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.2.233
更新日期:1993-02-01 00:00:00
abstract::Non-obese diabetic mice spontaneously develop a type 1 diabetes. The entry of leukocytes in the islets of Langerhans was studied in untreated and in irradiated mice. FITC-labeled cells from spleen, lymph nodes or bone marrow of healthy or diabetic donors did home to the inflamed islets of unmanipulated recipients. B a...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.12.1905
更新日期:1995-12-01 00:00:00
abstract::Mice lacking the IL-2 receptor beta chain (IL-2R beta) exhibit an autoimmune reaction characterized by generalized T cell activation, production of autoantibodies, myeloproliferation and severe anemia. T cells of IL-2R beta-/- mice were examined to elucidate the mechanism responsible for their abnormal activation and ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.9.1367
更新日期:1997-09-01 00:00:00
abstract::Intravenous sensitization of C57BL/6 (B6) mice with class II H-2-disparate B6-C-H-2bm12(bm12) resting B cells induced anti-bm12 CD4+ T cell tolerance as shown by hyporesponsiveness in the anti-bm12 mixed lymphocyte reaction (MLR). The present study investigated the mechanism(s) of the failure of bm12 B cells to stimul...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.2.159
更新日期:1996-02-01 00:00:00
abstract::It has proven difficult to evaluate the functional potential of germinal center (GC) B cells, including those from Peyer's patches (PP), by either in vivo or in vitro methods. Thus, rather than assess secreted Ig product as an indicator of functional potential we have instead sought to detect mRNAs related to the vari...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/3.12.1253
更新日期:1991-12-01 00:00:00
abstract::Fc receptors play important roles for a wide array of immune responses. In contrast to the well-defined Fcγ and Fcε receptors, the molecular and functional characteristics of Fc receptors for IgA and IgM have remained incompletely understood for years. Recent progress has unveiled the characteristics of Fc receptors f...
journal_title:International immunology
pub_type: 杂志文章,评审
doi:10.1093/intimm/dxx059
更新日期:2017-12-30 00:00:00
abstract::Sera of patients suffering from systemic lupus erythematosus (SLE) frequently contain oligoclonal IgG autoantibodies with high affinity for the ribosomal protein L7 (rpL7). The humoral autoimmune response to rpL7 apparently is driven by antigen and T cell dependent. In order to analyze the T cell response to rpL7 we c...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.2.125
更新日期:1999-02-01 00:00:00
abstract::Normal human sera contained 10-60 ng/ml of soluble membrane cofactor protein (MCP, CD46) whereas sera of > 50% of the cancer patients contained > 60 ng/ml. MCP purified by immunoaffinity chromatography from both normal and cancer patients' sera consisted of three bands of 56, 47 and 29 kDa on SDS-PAGE/immunoblotting. ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.5.727
更新日期:1995-05-01 00:00:00
abstract::It is well established that the bacterial superantigens bind to both TCR beta-chain and, with moderate affinity, to MHC class II molecules. Class II-bearing cells bind the superantigen and present the superantigen to T cells expressing certain TCR beta-chain variable region alleles. We have observed that the superanti...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.11.1721
更新日期:1995-11-01 00:00:00