Abstract:
:We have evaluated the capacity of a novel, nanoparticle-based tumor vaccine to eradicate established tumors in mice. C57BL/6 mice were intradermally (i.d.) inoculated with ovalbumin (OVA)-expressing EG-7 tumor cells. When the tumor size reached 7-8 mm, the tumor-bearing mice were i.d. injected near the tumor-draining lymph node (DLN) with liposomes encapsulated with unmethylated cytosine-phosphorothioate-guanine containing oligodeoxynucleotides (CpG-ODN) (CpG-liposomes) co-encapsulated with OVA. This vaccination protocol markedly prevented the growth of the established tumor mass and approximately 50% of tumor-bearing mice became completely cured. Tumor eradication correlated with the generation of OVA/H-2K(b)-tetramer(+) CTLs in the tumor DLN and at the tumor site with specific cytotoxicity toward EG-7 cells. Interestingly, tetramer(+) CTLs failed to be induced in lymph node-deficient Aly/Aly mice. Thus, tetramer(+) CTLs appeared to be generated in the tumor DLN and subsequently migrated into the tumor site. In vivo antibody blocking experiments revealed that CD8(+) T cells, but not CD4(+) T, NK or NKT cells, were the major effector cells mediating tumor eradication. CTL induction was also inhibited when vaccinated tumor-bearing mice were treated with both anti-IFN-alpha and anti-IFN-beta mAbs but not with anti-IFN-alpha or anti-IFN-beta mAb alone. Neither IFN-gamma(-/-) nor IL-12(-/-) mice showed impaired induction of tetramer(+) CTLs. Thus, these findings revealed that CpG-ODN-induced IFN-alpha/beta, but not IL-12 or IFN-gamma, is critical for the generation of tumor-specific CTLs in response to vaccination. These results highlight the potential utility of CpG-liposomes co-encapsulated with protein tumor antigens as therapeutic vaccines in cancer patients.
journal_name
Int Immunoljournal_title
International immunologyauthors
Wakita D,Chamoto K,Zhang Y,Narita Y,Noguchi D,Ohnishi H,Iguchi T,Sakai T,Ikeda H,Nishimura Tdoi
10.1093/intimm/dxh381subject
Has Abstractpub_date
2006-03-01 00:00:00pages
425-34issue
3eissn
0953-8178issn
1460-2377pii
dxh381journal_volume
18pub_type
杂志文章abstract::IL-12 is a cytokine produced by monocytes and Epstein-Barr virus-transformed B cells which initiates Th1 responses by inducing the development of CD4+, IFN-gamma producing Th1 T cells in mouse and human. We have previously reported that allergen-specific CD4+ Th2 T cell clones produce IFN-gamma, following activation b...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.7.1091
更新日期:1994-07-01 00:00:00
abstract::We have followed CD4 and CD8 TCR V beta repertoires during the acute phase of Trypanosoma cruzi infection in a resistant mouse strain (C57BL/6). No major changes were found in the V beta TCR distributions analyzed (covering roughly 40% of the TCR repertoire) in peripheral CD4 T lymphocytes, confirming the polyclonal n...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.3.387
更新日期:1994-03-01 00:00:00
abstract::We developed a novel approach to probe the molecular basis of TCR recognition of the MHC class I-peptide complex and to determine how constraints placed on peptide binding by the class I molecule influence T cell recognition. We synthesized peptide pairs derived from the N- and C-terminal regions of class I peptide li...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.1.81
更新日期:1997-01-01 00:00:00
abstract::The ileal Peyer's patch (PP) plays a central role in B cell development in young sheep and it is hypothesized that this B cell development occurs independent of extrinsic antigen and T cells. Therefore, it was of interest to examine ileal PP follicular (iPf) B cell responses to CD40 ligand, a molecule integral to T ce...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.3.369
更新日期:1995-03-01 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::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
更新日期:2005-11-01 00:00:00
abstract::The Ig heavy chain (IgH) locus is controlled by multiple regulatory sequences mapping both within the IgH transcription unit (E mu) and downstream (3') of IgH coding sequences (hs3a, hs1,2, hs3b and hs4). Enhancer knockout studies in mice have implicated E mu in the control of IgH variable region gene assembly, but si...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/13.8.1003
更新日期:2001-08-01 00:00:00
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
更新日期:1992-03-01 00:00:00
abstract::Rheumatic fever (RF) follows a throat infection with different M-serotypes of beta-hemolytic group A streptococci (GAS) and can affect different tissues, predominantly the heart. It is thought to be an autoimmune illness. Although histological examination of affected heart shows an infiltrate consisting mainly of T ce...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.8.1235
更新日期:1994-08-01 00:00:00
abstract::Transforming growth factor (TGF)-beta has been shown to stimulate isotype switching to IgA in cultures of lipopolysaccharide (LPS)-stimulated B cells. The induction of isotype switching is associated with the appearance of novel germline alpha transcripts that cannot be found in cultures stimulated with LPS alone. TGF...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.1.113
更新日期:1994-01-01 00:00:00
abstract::Dendritic cells (DCs) act as a first-line recognition system for invading pathogens, such as influenza A. The interaction of DC with influenza A virus results in DC activation via endosomal Toll-like receptors and also leads to presentation of viral peptides on MHC class II molecules. Prior work demonstrated that infl...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxm030
更新日期:2007-05-01 00:00:00
abstract::MicroRNAs 125a and 125b are predicted to be able to bind to the B lymphocyte-induced maturation protein-1 (BLIMP-1) and IFN regulatory protein-4 (IRF-4) transcription factors, which are essential for plasma cell differentiation. A computational survey of the human and mouse genomes revealed that miR-125a and miR-125b ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxq042
更新日期:2010-07-01 00:00:00
abstract::pp56lck is a member of the src family of tyrosine kinases mainly expressed in T lymphocytes. Src tyrosine kinases have been implicated in the control of cell growth and differentiation in different cell types, but the mechanism of regulation of these enzymes is poorly understood. In order to characterize the distinct ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/3.7.673
更新日期:1991-07-01 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::Intestinal intraepithelial lymphocytes (i-IEL) of aged rats comprise CD4+CD8alphaalpha+ and CD4-CD8alphaalpha+ T cells expressing TCR alphabeta. In the present study, we compared characteristics between CD4+CD8alphaalpha+ and CD4-CD8alphaalpha+ i-IEL, which were purified by a cell sorter from the i-IEL of 6-month-old ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.1.21
更新日期:1999-01-01 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::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::The two-signal model states that activation of naive T cells requires a signal 1 stimulus through the TCR and a co-stimulatory signal 2. By contrast, signal 1 alone is sufficient for pre-activated T cells. Recently, however, it has been shown that under certain conditions T cells can bypass the requirement for co-stim...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.5.619
更新日期:1998-05-01 00:00:00
abstract::Animal models of autoimmune diseases have been instrumental in advancing our understanding of autoimmunity in humans. Collagen-induced arthritis in mice is an autoimmune disease model of rheumatoid arthritis, which is MHC class II restricted and CD4 T cell dependent. To better understand the fundamental role of T cell...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.11.1613
更新日期:1998-11-01 00:00:00
abstract::Incompatibility of human minor histocompatibility (hmH) antigens induces rejection of grafts in organ transplantation and graft versus host disease in bone marrow transplantation if donor and recipient are matched for human leukocyte antigen (HLA) genes. These antigens are recognized only by T cells. We describe here ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/4.2.301
更新日期:1992-02-01 00:00:00
abstract::Recent studies point to glycolipid-enriched membrane (GEM) microdomains as the critical sites for TCR-mediated signal transduction. However, whether the TCR complex is localized in the GEM domain is not well-defined. In the present study, we analyzed localization of the TCR-CD3 complex in the GEM domain by isolating t...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.9.1395
更新日期:1999-09-01 00:00:00
abstract::The CD2 co-receptor expressed on the surface of T lymphocytes is able to stimulate T cell activation, proliferation and cytokine production in the absence of direct engagement of the antigen-specific TCR. Engagement of human CD2 by mitogenic pairs of anti-CD2 mAb induces tyrosine phosphorylation of a number of intrace...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/13.1.13
更新日期:2001-01-01 00:00:00
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
更新日期:1998-08-01 00:00:00
abstract::To investigate the involvement of retinoic acid receptor (RAR)-alpha in allograft rejection, we investigated the effect of a novel selective agonist to the receptor, ER-38925, in a mouse cardiac allograft model. Prophylactic treatment with ER-38925 inhibited the acute rejection of the mouse cardiac allograft (BALB/c -...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh066
更新日期:2004-05-01 00:00:00
abstract::Incomplete T cell antigen receptor-mediated signaling induces an unresponsive state known as anergy. Previously, we had shown that anergy can be induced in antigen-primed but not naive T cells. In this report, we found that in vitro primed T cells from IL-2R alpha-deficient mice were resistant to anergy induction in c...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh397
更新日期:2006-05-01 00:00:00
abstract::The class II trans-activator (CIITA) is a bi- or multi-functional domain protein which plays a critical role in the expression of MHC class II genes. We report that removal of the N-terminal 151 amino acids, encompassing all of the acidic domain but leaving intact the proline/serine/threonine-rich domain, results in a...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.10.1545
更新日期:1997-10-01 00:00:00
abstract::We have generated a high copy number transgenic mouse line in which expression of mouse IL-7 cDNA is under the control of the mouse MHC class II E alpha promoter. These mice were generated in order to see if IL-7 over-production in the thymus altered either thymocyte differentiation or the process of negative selectio...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.3.401
更新日期:1995-03-01 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::Using Ia antigen-containing lipid vesicles, we investigated by stopped-flow fluorometry the requirements for helper T cell recognition and activation. When azobenzenearsonate-L-tyrosine (ABA-L-Tyr)-specific, I-Ak-restricted helper T cell hybridomas 2-45-12 were mixed with ABA-L-Tyr and purified I-Ak molecules on lipid...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/2.6.509
更新日期:1990-01-01 00:00:00
abstract::The extracellular signal-regulated kinase (ERK) signaling pathway is strongly activated in response to TCR stimulation in normal T cells. However, the extent to which activation of the ERK pathway is necessary for TCR-stimulated cytokine production is not clear. We have addressed this question by use of two separate m...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.2.223
更新日期:1998-02-01 00:00:00