Induction of human humoral immune responses in a novel HLA-DR-expressing transgenic NOD/Shi-scid/γcnull mouse.

Abstract:

:Mounting evidence has demonstrated that NOD-Shi/scid/γc(null) (NOG) mice are one of the most suitable mouse strains for humanized mouse technologies, in which various human cells or tissues can be engrafted without rejection and autonomously maintained. We have characterized and analyzed various features of the human immune system reconstituted in NOG mice by transplanting human hematopoietic stem cells (hu-HSC). One of the problems of the quasi-immune system in these hu-HSC NOG mice is that the quality of immune responses is not always sufficient, as demonstrated by the lack of IgG production in response to antigen challenge. In this study, we established a novel transgenic NOG sub-strain of mice bearing the HLA-DRA and HLA-DRB1:0405 genes, which specifically expresses HLA-DR4 molecules in MHC II-positive cells. This mouse strain enabled us to match the haplotype of HLA-DR between the recipient mice and human donor HSC. We demonstrated that T-cell homeostasis was differentially regulated in HLA-matched hu-HSC NOG mice compared with HLA-mismatched control mice, and antibody class switching was induced after immunization with exogenous antigens in HLA-matched mice. This novel mouse strain improves the reconstituted human immune systems that develop in humanized mice and will contribute to future studies of human humoral immune responses.

journal_name

Int Immunol

journal_title

International immunology

authors

Suzuki M,Takahashi T,Katano I,Ito R,Ito M,Harigae H,Ishii N,Sugamura K

doi

10.1093/intimm/dxs045

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

243-52

issue

4

eissn

0953-8178

issn

1460-2377

pii

dxs045

journal_volume

24

pub_type

杂志文章
  • Mucolipin 1 positively regulates TLR7 responses in dendritic cells by facilitating RNA transportation to lysosomes.

    abstract::Toll-like receptor 7 (TLR7) and TLR9 sense microbial single-stranded RNA (ssRNA) and ssDNA in endolysosomes. Nucleic acid (NA)-sensing in endolysosomes is thought to be important for avoiding TLR7/9 responses to self-derived NAs. Aberrant self-derived NA transportation to endolysosomes predisposes to autoimmune diseas...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxu086

    authors: Li X,Saitoh S,Shibata T,Tanimura N,Fukui R,Miyake K

    更新日期:2015-02-01 00:00:00

  • Loss of MHC II ubiquitination inhibits the activation and differentiation of CD4 T cells.

    abstract::Peptide-MHC class II complexes (pMHC II) are degraded by MARCH-I-mediated ubiquitination, and the stabilization of pMHC II by loss of its ubiquitination is one phenotype defining the activation of conventional dendritic cells (cDCs). However, the role of such stabilization of pMHC II in the context of T-cell activatio...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxt066

    authors: Ishikawa R,Kajikawa M,Ishido S

    更新日期:2014-05-01 00:00:00

  • Interleukin 6 in inflammation, autoimmunity and cancer.

    abstract::Interleukin 6 (IL-6) is involved both in immune responses and in inflammation, hematopoiesis, bone metabolism and embryonic development. IL-6 plays roles in chronic inflammation (closely related to chronic inflammatory diseases, autoimmune diseases and cancer) and even in the cytokine storm of corona virus disease 201...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxaa078

    authors: Hirano T

    更新日期:2020-12-18 00:00:00

  • The P9 pocket of HLA-DQ2 (non-Aspbeta57) has no particular preference for negatively charged anchor residues found in other type 1 diabetes-predisposing non-Aspbeta57 MHC class II molecules.

    abstract::Susceptibility and resistance to type 1 diabetes are associated with MHC class II alleles that carry non-Asp and Asp at residue 57 of their beta chain respectively. The effect of Asp or non-Aspbeta57 may relate to a differential ability of distinct class II molecules to bind specific immuno-pathogenic peptides. Recent...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/10.8.1229

    authors: Quarsten H,Paulsen G,Johansen BH,Thorpe CJ,Holm A,Buus S,Sollid LM

    更新日期:1998-08-01 00:00:00

  • Analysis of stem-cell-like properties of human CD161++IL-18Rα+ memory CD8+ T cells.

    abstract::CD161(++)IL-18Rα(+)CD8(+) human T cells have recently been identified as a new subset of memory cells but their exact role remains unclear. CD161(++)IL-18Rα(+)CD8(+), mucosal-associated invariant T cells express a semi-invariant TCR Vα7.2-Jα33, which recognizes the MHC-related protein 1. On the basis of properties inc...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxs069

    authors: Havenith SH,Yong SL,Henson SM,Piet B,Idu MM,Koch SD,Jonkers RE,Kragten NA,Akbar AN,van Lier RA,ten Berge IJ

    更新日期:2012-10-01 00:00:00

  • Influence of HLA-DR2, HLA-DPw4, and T cell receptor alpha chain genes on the susceptibility to multiple sclerosis.

    abstract::In view of our recent report that T cell receptor (TCR) alpha chain restriction fragment length polymorphism (RFLP) is associated with multiple sclerosis (MS), we have assessed the possibility that HLA-DR2, HLA-DPw4, and TCR alpha chain RFLPs may interact to increase the risk of developing MS. Detection of TCR alpha c...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/4.2.177

    authors: Sherritt MA,Oksenberg J,de Rosbo NK,Bernard CC

    更新日期:1992-02-01 00:00:00

  • CD4-CD8- thymocytes that express the T cell receptor may have previously expressed CD8.

    abstract::Amongst CD4-CD8- (double negative) thymocytes there is a sizeable population (variable from strain to strain) of cells expressing surface T cell receptor (TCR). These TCR+ double negatives are predominantly non-cycling, have very little precursor activity, and, unlike the TCR-CD4-CD8- thymocytes, appear not to be part...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/2.1.51

    authors: Wu L,Pearse M,Egerton M,Petrie H,Scollay R

    更新日期:1990-01-01 00:00:00

  • A self peptide naturally presented by both H-2Kb and H-2Kbm1 molecules demonstrates MHC restriction of self tolerance at the molecular level.

    abstract::An alloreactive CTL clone, 27.B2, produced in the mouse strain combination B6.C-H-2bm1 (bm1) against C57BL/6 (B6) and nominally directed against the Kb molecule has been shown to be peptide dependent. The clone recognizes intact B6, but not intact bm1 or bm3 target cells. However, peptides recognized by 27.B2 CTL can ...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/4.3.321

    authors: Falk K,Rötzschke O,Rammensee HG

    更新日期:1992-03-01 00:00:00

  • The role of immune cells in brain development and neurodevelopmental diseases.

    abstract::During brain development, the generation of neurons and glial cells is rigorously regulated by diverse mechanisms including the immune system. Dysfunction of the developing system results in the onset of neurodevelopmental disorders and psychological disorders. Recent studies have demonstrated that the immune system i...

    journal_title:International immunology

    pub_type: 杂志文章,评审

    doi:10.1093/intimm/dxy041

    authors: Tanabe S,Yamashita T

    更新日期:2018-09-25 00:00:00

  • Negative autoregulation of Src homology region 2-domain-containing phosphatase-1 in rat basophilic leukemia-2H3 cells.

    abstract::Src homology region 2-domain-containing phosphatase-1 (SHP-1) plays an important role in the regulation of signaling from various receptors in hematopoietic cells. In mast cells, SHP-1 has been shown to negatively regulate the initial signaling triggered by high-affinity receptor for IgE (FcepsilonRI) and positively r...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxm070

    authors: Ozawa T,Nakata K,Mizuno K,Yakura H

    更新日期:2007-09-01 00:00:00

  • B-lineage cell deficits in bone marrow of lpr/lpr mice.

    abstract::Analyses of bone marrow (BM) lymphocytes in C57BL/6 mice homozygous for the lpr mutation (B6.lpr) disclosed low numbers of pre-B and B cells, as compared with age-matched control B6 mice. BM depletion in B6.lpr mice was selective for B-lineage cells, appeared in young adults, and developed markedly with age and diseas...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/8.2.247

    authors: Sundblad A,Coutinho A

    更新日期:1996-02-01 00:00:00

  • Expression of multilectin receptors and comparative FITC-dextran uptake by human dendritic cells.

    abstract::Dendritic cells (DC) are potent antigen-presenting cells and understanding their mechanisms of antigen uptake is important for loading DC with antigen for immunotherapy. The multilectin receptors, DEC-205 and macrophage mannose receptor (MMR), are potential antigen-uptake receptors; therefore, we examined their expres...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/12.11.1511

    authors: Kato M,Neil TK,Fearnley DB,McLellan AD,Vuckovic S,Hart DN

    更新日期:2000-11-01 00:00:00

  • Role of the CD5 molecule on TCR gammadelta T cell-mediated immune functions: development of germinal centers and chronic intestinal inflammation.

    abstract::Although CD4(+) T cells form a major subset of TCRalphabeta T cells, only a small number of TCRgammadelta T cells express CD4. Factors contributing to the down-regulation of CD4(+) TCRgammadelta T cells have not been identified. The CD5 molecule is expressed on most TCRgammadelta T cells in the spleen, whereas only a ...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxg006

    authors: Mizoguchi A,Mizoguchi E,de Jong YP,Takedatsu H,Preffer FI,Terhorst C,Bhan AK

    更新日期:2003-01-01 00:00:00

  • Novel NLRP3/cryopyrin mutations and pro-inflammatory cytokine profiles in Behçet's syndrome patients.

    abstract::Behçet's syndrome (BS) is a systemic inflammatory disorder with unknown etiology. Features of both innate and adaptive immunity have been claimed in the pathogenesis of BS. To test the possible dysregulation of the NLRP3/cryopyrin (Nod-like receptor with a pyrin domain 3) inflammasome, as a result of mutation(s), we p...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxt046

    authors: Yüksel Ş,Eren E,Hatemi G,Sahillioğlu AC,Gültekin Y,Demiröz D,Akdiş C,Fresko İ,Özören N

    更新日期:2014-02-01 00:00:00

  • FOXP3 is a homo-oligomer and a component of a supramolecular regulatory complex disabled in the human XLAAD/IPEX autoimmune disease.

    abstract::We have found that FOXP3 is an oligomeric component of a large supramolecular complex. Certain FOXP3 mutants with single amino acid deletions in the leucine zipper domain of FOXP3 are associated with the X-linked autoimmunity-allergic dysregulation (XLAAD) and immunodysregulation, polyendocrinopathy and enteropathy, X...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxm043

    authors: Li B,Samanta A,Song X,Iacono KT,Brennan P,Chatila TA,Roncador G,Banham AH,Riley JL,Wang Q,Shen Y,Saouaf SJ,Greene MI

    更新日期:2007-07-01 00:00:00

  • Transforming growth factor-beta 1 enhances IgG and IgA sheep red blood cell responses.

    abstract::Antibody responses to ingested antigens can be inhibited by a mechanism known as oral tolerance which acts to prevent excessive stimulation from luminal contents. Local IgA responses can be induced in this non-responsive environment and during intestinal inflammation, mucosal IgG responses can also be increased. The p...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/4.9.975

    authors: Zettel L,Clark DA,Ernst PB

    更新日期:1992-09-01 00:00:00

  • Inhibition of experimental autoimmune encephalomyelitis in Lewis rats by nasal administration of encephalitogenic MBP peptides: synergistic effects of MBP 68-86 and 87-99.

    abstract::Induction of mucosal tolerance by inhalation of soluble peptides with defined T cell epitopes is receiving much attention as a means of specifically down-regulating pathogenic T cell reactivities in autoimmune and allergic disorders. Experimental autoimmune encephalomyelitis (EAE) induced in the Lewis rat by immunizat...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/10.8.1139

    authors: Liu JQ,Bai XF,Shi FD,Xiao BG,Li HL,Levi M,Mustafa M,Wahren B,Link H

    更新日期:1998-08-01 00:00:00

  • Partial rescue of B cells in microphthalmic osteopetrotic marrow by loss of response to type I IFNs.

    abstract::The microphthalmic (mi) mouse exhibits deficiencies in the development of osteoclasts, melanocytes, mast cells and marrow B cells. Previously, we demonstrated that the marrow of such mice over-express receptor activator of nuclear factor kappaB (RANK) ligand (RANKL). RANKL has been shown to induce the production of IF...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxh327

    authors: Roundy KM,Spangrude G,Weis JJ,Weis JH

    更新日期:2005-11-01 00:00:00

  • Molecular cloning and characterization of guinea pig Fc gamma RIII: expression but not function is independent of the gamma chain of Fc epsilon RI.

    abstract::We have isolated two cDNA clones encoding the guinea pig receptor for the Fc portion of IgG2 (Fc gamma 2R) from a guinea pig peritoneal macrophage cDNA library. Analysis of the predicted amino acid sequence of the one cDNA clone indicated that the guinea pig Fc gamma 2R is a type I transmembrane protein and has approx...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/8.9.1335

    authors: Isashi Y,Yamashita T,Nagasawa S,Murakami M,Uede T

    更新日期:1996-09-01 00:00:00

  • Molecular basis of the synergistic production of IL-1 receptor antagonist by human neutrophils stimulated with IL-4 and IL-10.

    abstract::In this study, we report that the release of IL-1 receptor antagonist (IL-1ra) from IL-4-stimulated neutrophils is markedly enhanced in the presence of IL-10. We also show that up-regulation of IL-1ra release by IL-10 in IL-4-stimulated neutrophils takes place through IL-1ra mRNA stabilization and enhancement of IL-1r...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxf079

    authors: Crepaldi L,Silveri L,Calzetti F,Pinardi C,Cassatella MA

    更新日期:2002-10-01 00:00:00

  • Immunoblot analysis of cellular expression of Bcl-2 family proteins, Bcl-2, Bax, Bcl-X and Mcl-1, in human peripheral blood and lymphoid tissues.

    abstract::The ability of Bcl-2 to inhibit apoptotic cell death is well established. Several homologues of the bcl-2 gene, such as bax, bcl-x or mcl-1, have recently been identified. Like Bcl-2, both Bcl-XL and Mcl-1 appear to function as repressors of apoptotic cell death, whereas Bax facilitates it, indicating possible interac...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/7.11.1817

    authors: Ohta K,Iwai K,Kasahara Y,Taniguchi N,Krajewski S,Reed JC,Miyawaki T

    更新日期:1995-11-01 00:00:00

  • Ig heavy chain class switching in Rag-deficient mice.

    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

    authors: Lansford R,Manis JP,Sonoda E,Rajewsky K,Alt FW

    更新日期:1998-03-01 00:00:00

  • Modeling the presentation of C3d-coated antigen by B lymphocytes: enhancement by CR1/2-BCR co-ligation is selective for the co-ligating antigen.

    abstract::We have used a set of single-chain variable fragment antibodies (sc) genetically fused with an influenza hemagglutinin-derived peptide as a means to investigate the role of CR1 and CR2 in antigen presentation by B cells. When incubated with the B cell lymphoma 2PK3, peptide-containing sc specific for either CR1 or CR1...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/14.3.241

    authors: Prechl J,Baiu DC,Horváth A,Erdei A

    更新日期:2002-03-01 00:00:00

  • Arthritis and pneumonitis produced by the same T cell clones from mice with spontaneous autoimmune arthritis.

    abstract::SKG mice, a newly established model of rheumatoid arthritis (RA), spontaneously develop autoimmune arthritis accompanying extra-articular manifestations, such as interstitial pneumonitis. To examine possible roles of T cells for mediating this systemic autoimmunity, we generated T cell clones from arthritic joints of ...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxn091

    authors: Wakasa-Morimoto C,Toyosaki-Maeda T,Matsutani T,Yoshida R,Nakamura-Kikuoka S,Maeda-Tanimura M,Yoshitomi H,Hirota K,Hashimoto M,Masaki H,Fujii Y,Sakata T,Tsuruta Y,Suzuki R,Sakaguchi N,Sakaguchi S

    更新日期:2008-10-01 00:00:00

  • NADPH diaphorase staining suggests a transient and localized contribution of nitric oxide to host defence against an intracellular pathogen in situ.

    abstract::Nitric oxide (NO) is formed constitutively in neurons by the constitutive enzyme NO synthase (cNOS) and acts as a neurotransmitter. It has already been shown that cNOS-containing neurons are identical to neurons staining for NADPH diaphorase and vice versa. Effector cells of the immune response produce high NO levels ...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/6.11.1751

    authors: Flesch IE,Hess JH,Kaufmann SH

    更新日期:1994-11-01 00:00:00

  • Glycosyltransferase regulation mediated by pre-TCR signaling in early thymocyte development.

    abstract::CT1 is a carbohydrate moiety of CD45 that is expressed on fetal thymocytes in vivo. Examination of CT1 expression on thymocyte subsets revealed that primarily pro-T cells (CD44+ CD25+) and pre-T cells (CD44- CD25+) expressed CT1. Interestingly, non-T-lineage committed lymphoid progenitors (CD44+ CD25-) lacked CT1 indi...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/10.4.445

    authors: Reed DS,Olson S,Lefrançois L

    更新日期:1998-04-01 00:00:00

  • Loss of SDF-1 receptor expression during positive selection in the thymus.

    abstract::SDF-1 is a member of the CXC chemokines. In contrast to other chemokines that are induced by inflammation, SDF-1 is constitutively produced by stromal cells. In order to investigate the physiological roles of SDF-1, we constructed a fusion protein, SDF-1-Cgamma1, composed from murine SDF-1alpha and the constant region...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/10.8.1049

    authors: Suzuki G,Nakata Y,Dan Y,Uzawa A,Nakagawa K,Saito T,Mita K,Shirasawa T

    更新日期:1998-08-01 00:00:00

  • Host chemokine (C-C motif) ligand-2 (CCL2) is differentially regulated in HIV type 1 (HIV-1)-infected individuals.

    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

    authors: Ansari AW,Bhatnagar N,Dittrich-Breiholz O,Kracht M,Schmidt RE,Heiken H

    更新日期:2006-10-01 00:00:00

  • Neonatal treatment with monoclonal natural antibodies restores a normal pattern of VH gene utilization in the non-obese diabetic mouse.

    abstract::The utilization of individual VH7183 genes in the autoimmune non-obese diabetic (NOD) mouse and the normal C57BL/6 mouse, both carrying the IgHb haplotype, was investigated. Nucleotide sequence analyses of a large number of VHDJH rearrangements utilizing VH7183 gene segments allowed us to identify 10 individual member...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/6.4.623

    authors: Andersson A,Ekstrand-Hammarström B,Eriksson B,Overmo C,Holmberg D

    更新日期:1994-04-01 00:00:00

  • CD28 co-stimulatory signals induce IL-2 receptor expression on antigen-stimulated virgin T cells by an IL-2-independent mechanism.

    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

    authors: Toyooka K,Maruo S,Iwahori T,Yamamoto N,Tai XG,Abe R,Takahama Y,Murakami M,Uede T,Hamaoka T,Fujiwara H

    更新日期:1996-02-01 00:00:00