International Immunology (INT IMMUNOL )

Publisher: Oxford University Press

Description

International Immunology publishes a broad range of experimental and theoretical studies in molecular and cellular immunology conducted in laboratories throughout the world.

Impact factor 3.18

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    Impact factor
  • 5-year impact
    3.23
  • Cited half-life
    8.40
  • Immediacy index
    0.41
  • Eigenfactor
    0.01
  • Article influence
    1.36
  • Website
    International Immunology website
  • Other titles
    International immunology online., International immunology
  • ISSN
    0953-8178
  • OCLC
    20567176
  • Material type
    Periodical, Internet resource
  • Document type
    Journal / Magazine / Newspaper, Internet Resource

Publisher details

Oxford University Press

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months embargo on science, technology, medicine articles
    • 2 years embargo on arts and humanities articles
    • Some titles may have different embargoes
  • Conditions
    • Pre-print can only be posted prior to acceptance
    • Pre-print must be accompanied by set statement (see link)
    • Pre-print must not be replaced with post-print, instead a link to published version with amended set statement should be made
    • Pre-print on author's personal website, employer website, free public server or pre-prints in subject area
    • Post-print in Institutional repositories or Central repositories
    • Publisher version cannot be used except for Nucleic Acids Research articles
    • Published source must be acknowledged
    • Must link to publisher version
    • Set phrase to accompany archived copy (see policy)
    • Articles in some journals can be made Open Access on payment of additional charge
    • Eligible UK authors may deposit in OpenDepot
    • Publisher will deposit on behalf of NIH funded authors to PubMed Central, Nucleic Acids Research authors must pay their fee first
    • Some titles may use different policies
  • Classification
    ​ yellow

Publications in this journal

  • International Immunology 01/2015; 27(1):1-2.
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    ABSTRACT: The respiratory syncytial virus (RSV) is responsible for as many as 199,000 annual deaths worldwide. Currently there is no standard treatment for RSV disease, and no vaccine. Sendai virus is an attractive pediatric vaccine candidate because it elicits robust and long-lasting virus-specific B cell and T cell activities in systemic and mucosal tissues. The virus serves as a gene delivery system as well as a Jennerian vaccine against its close cousin, human parainfluenza virus type 1. Here is described the testing of a recombinant SeV (SeVRSV-Fs) that expresses an unconstrained, secreted RSV-F protein as a vaccine against RSV in cotton rats. After a single intranasal immunization of cotton rats with SeVRSV-Fs, RSV-specific binding and neutralizing antibodies were generated. These antibodies exhibited cross-reactivity with both RSV A and B isolates. RSV-F-specific interferon-γ-producing T cells were also activated. The SeVRSV-Fs vaccine conferred complete protection against RSV challenge without enhanced immunopathology. In total, results showed that an SeV recombinant that expresses RSV F in an unconstrained, soluble form can induce humoral and cellular immunity that protects against infection with RSV. © The Japanese Society for Immunology. 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    International Immunology 12/2014;
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    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 in mice deficient in Zap70, Slp76, Lat, or Vav1, indicating the presence of alternative pathways normally suppressed by Cbl. To further elucidate pre-TCR/TCR signaling pathways involved in thymic development, we characterized the effect of Cbl inactivation on developmental and signaling defects in mice deficient in proximal signaling molecules Lck and Zap70. Inactivation of Cbl partially reversed defective T cell development in Zap70(-/-) mice and reversed defects in phosphorylation of Erk, Plc-γ1, Vav1, and Akt, in TCR-stimulated Cbl(-/-)Zap70(-/-) thymocytes. Recent reports identified an essential role of Lck in associating with CD4 and CD8 coreceptors and mediating the requirement for MHC restriction in TCR recognition. Since TCR recognition has been shown to be MHC-restricted in Cbl(-/-) mice, it was of interest to determine whether the requirement for Lck remained unmodified by Cbl deletion, Indeed, in contrast to the effect of Cbl inactivation in partially or fully bypassing requirements for other TCR signaling components, inactivation of Cbl did not reverse either defective T cell developmental or defective phosphorylation of TCR signaling molecules in Lck(-/-) mice. Thus, Lck, which plays a unique role in enforcing MHC restriction, is essential for thymic development in presence or absence of Cbl, ensuring MHC restriction of T cells derived from either pathway. Published by Oxford University Press on behalf of The Japanese Society for Immunology 2014.
    International Immunology 12/2014;
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    ABSTRACT: If Bcl11b activity is compromised, CD4(+)CD8(+) double-positive (DP) thymocytes produce a greatly increased fraction of innate CD8(+) single-positive (SP) cells highly producing IFN-γ, which are also increased in mice deficient of genes such as Itk, Id3 and NF-κB1 that affect TCR signaling. Of interest, the increase in the former two is due to the bystander effect of IL-4 that is secreted by PLZF-expressing NKT and γδT cells whereas the increase in the latter is cell intrinsic. Bcl11b zinc-finger proteins play key roles in T cell development and T cell-mediated immune response likely through TCR signaling. We examined thymocytes at and after the DP stage in Bcl11b(F/S826G) CD4cre, Bcl11b(F/+) CD4cre, and Bcl11b(+/S826G) mice, carrying the allele that substituted serine for glycine at the position of 826. Here we show that Bcl11b impairment leads to an increase in the population of TCRαβ(high)CD44(high)CD122(high) innate CD8SP thymocytes, together with two different developmental abnormalities: impaired positive and negative selection accompanying a reduction in the number of CD8SP cells, and developmental arrest of NKT cells at multiple steps. The innate CD8SP thymocytes express Eomes and secrete IFN-γ after the stimulation with PMA and ionomycin, and in this case their increase is not due to a bystander effect of IL-4 but cell intrinsic. Those results indicate that Bcl11b regulates development of different thymocyte subsets at multiple stages and prevents the excess of innate CD8SP thymocytes. © The Japanese Society for Immunology. 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    International Immunology 11/2014;
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    ABSTRACT: Endometriosis is a significant debilitating gynecological problem affecting women of reproductive age group and post-menopause. Recent reports prompt at the role of endometriotic Mesenchymal Stem Cells (ectopic MSCs) in pathogenesis of endometriosis. To investigate the plausible mechanisms leading to the pathogenic behavior of ectopic MSCs, we compared the immunomodulatory properties of eutopic and ectopic (healthy) MSCs. We analyzed MSC phenotypes, differential gene expression for an array of pattern recognition receptors (PRRs) and pro-inflammatory cytokine release along with markers of migration and angiogenesis among eutopic and ectopic MSCs. Further, alterations in immunosuppressive functions of eutopic and ectopic MSCs were examined by co-culturing them with mitogen-activated allogenic PBMCs. Transcripts of PRRs such as all Toll-like Receptors (TLR 1-10), except TLR8, collectins (CL-L1, CL-P1, CL-K1), NOD-1 and 2 receptors, secreted pro-inflammatory cytokines like IL-6, IFNγ, VEGF, EGF, MCP-1 were significantly upregulated in ectopic MSCs. The anti-inflammatory cytokine TGFβ showed significant downregulation, while IL-10 showed a significant increase in ectopic MSCs. Further, ectopic MSCs showed upregulated expression for markers of migration and angiogenesis such as MMP - 2, 3, 9 and VEGF respectively. We report here that proliferation of PBMCs was less inhibited upon co-culture with ectopic MSCs compared with eutopic MSCs. The findings suggest that ectopic MSCs with increased levels of TLRs, collectins, pro-inflammatory cytokines and markers of migration and angiogenesis, exhibit a distinct immune-phenotype compared to eutopic MSCs. This distinct phenotype may be responsible for the reduced immunosuppressive property of ectopic MSCs and may be associated with the pathogenesis of endometriosis. © The Japanese Society for Immunology. 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    International Immunology 11/2014;
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    ABSTRACT: While for a century therapeutics has been dominated by small molecules organic chemicals of ~ 400 daltons absorbable via the gut, this is no longer the case. There are now a plethora of important medicines which are proteins, and injectable which have dramatically improved the therapy of many inflammatory diseases and of cancer. Most of these are monoclonal antibodies, some are receptor Ig Fc fusion proteins, others are cytokines or enzymes. The key to this new aspect of therapeutics has been the filling of unmet needs, and the consequent commercial success, which promoted further research and development. The first 'biologic' for a common disease, rheumatoid arthritis (RA) was a monoclonal antibody to human TNF, infliximab. This was based on our work, which is described in this review, summarising how TNF was defined as a good target in RA, how it was developed is described here, as well as future indications for antiTNF and related agents. Biologics are now the fastest growing sector of therapeutics. © The Japanese Society for Immunology. 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    International Immunology 11/2014;
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    ABSTRACT: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder of the exocrine glands with associated lymphocytic infiltrates of the affected glands. Dryness of the mouth and eyes results from involvement of the salivary and lacrimal glands. Efficacy of Rituximab (RTX) in pSS is still open to debate. This study delineates the signalling pathway involved in RTX-mediated pro-inflammatory factors down-regulation in a co-culture system of pSS salivary gland epithelial cells (SGEC) with syngeneic pSS B-lymphocytes. In addition, the effects of RTX on the Raf-1/ERK1/2 pathway activation in pSS SGEC co-cultured with syngeneic pSS T-lymphocytes were also investigated. This study demonstrated that RTX may interfere with the ERK1/2 pathway in a syngeneic co-culture of pSS SGEC with pSS B lymphocytes, leading to decreased cytokines production by SGEC. These novel findings reveal that syngeneic co-culture of pSS SGEC with pSS B lymphocytes leads to a down-regulation of Raf-1 in epithelial cells that adversely regulates the activity of the ERK1/2 pathway and determines a subsequent reduction of the pro-inflammatory factors release.
    International Immunology 11/2014;
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    ABSTRACT: G protein-coupled receptor 55 (GPR55) is activated by endogenous, plant-derived and synthetic cannabinoids. Recent studies reported a broad tissue distribution for GPR55 and found prominent roles for this receptor in inflammatory pain, gut and bone physiology, as well as cancer. However, little is known about the expression and function of GPR55 in immune cells. To address this question, we performed a detailed characterization of GPR55 in different human innate and adaptive immune populations using polychromatic flow cytometry and we found that monocytes and NK cells expressed remarkable levels of this receptor compared to several cells of adaptive immunity. GPR55 activation by the specific agonist O-1602 boosted IL-12 and TNF-α production, and increased endocytic activity, in LPS-activated monocytes. In addition, it increased CD69 activation marker expression, granzyme B and CD107a-dependent cytotoxicity, IFN-γ and TNF-α production in NK cells activated by both IL-2 and IL-12. These over-stimulatory effects of GPR55 were antagonized by its selective antagonist cannabidiol (CBD). Altogether, our data thus unveil a proinflammatory role for GPR55 in innate immunity that may be important for the design of new immune therapeutic strategies.
    International Immunology 10/2014;
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    ABSTRACT: The immune system is inextricably linked with many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), a devastating neuromuscular disorder affecting motor cell function with an average survival of 3 years from symptoms onset. In ALS there is a dynamic interplay between the resident innate immune cells, i.e. microglia and astrocytes, which may become progressively harmful to motor neurons. While innate and adaptive immune responses are associated with progressive neurodegeneration, in the early stages of ALS immune activation pathways are primarily considered to be beneficial promoting neuronal repair of the damaged tissues, though a harmful effect of T cells at this stage of disease has also been observed. In addition, while autoantibodies against neuronal antigens are present in ALS, it is unclear whether these arise as a primary or secondary event to neuronal damage, and whether the autoantibodies are indeed pathogenic. Understanding how the immune system contributes to the fate of motor cells in ALS may shed light on the triggers of disease as well as on the mechanisms contributing to the propagation of the pathology. Immune markers may also act as biomarkers while pathways involved in immune action may be targets of new therapeutic strategies. Here, we review the modalities by which the immune system senses the core pathological process in motor neuron disorders, focussing on tissue-specific immune responses in the neuromuscular junction and in the neuroaxis observed in affected individuals and in animal models of ALS. We elaborate on existing data on the immunological fingerprint of ALS that could be used to identify clues on the disease origin and patterns of progression.
    International Immunology 10/2014;
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    ABSTRACT: Allergic contact dermatitis (ACD) is one of typical occupational diseases in industrialized countries. Although various cytokines and chemokines are suggested to be involved in the pathogenesis of ACD, the roles of these molecules remain to be elucidated. CC chemokine receptor 8 (CCR8) is one of such molecules, of which expression is up-regulated in inflammatory sites of ACD patients. In this study, we found that Ccr8(-/-) mice developed severer contact hypersensitivity (CHS) responses to 2,4-dinitrofluorobenzene, a murine model of ACD, compared to wild-type mice. T cells from Ccr8(-/-) mice showed enhanced proliferative recall responses and Th1 and Th17 cell populations were expanded in these mice. However, CHS responses were similar between SCID mice adoptively transferred with Ccr8(-/-) and WT T cells, suggesting that CCR8 in T cells is not responsible for the exacerbation of CHS. Notably, skin-resident dendritic cells (DCs), such as Langerhans cells and dermal DCs, and inflammatory DCs were highly accumulated in lymph nodes (LNs) of Ccr8(-/-) mice after sensitization. Consistent with this, Ccr8(-/-) antigen presenting cells readily migrated from the skin to the draining LNs after sensitization. These observations suggest that CCR8 negatively regulates migration of cutaneous DCs from the skin to the draining LNs in CHS by keeping these cells in the skin.
    International Immunology 10/2014;
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    ABSTRACT: Multiple Sclerosis (MS) is a disorder of putative autoimmune origin, where immune cells invade the central nervous system and cause damage by attacking the myelin sheath of nerve cells. The blockade of the integrin very-late-antigen-4 (VLA-4) with the monoclonal antibody natalizumab has become the most effective therapy against MS since its approval in 2004. It is assumed that the inhibition of VLA-4-mediated immune cell adhesion to the endothelium of the blood-brain-barrier alleviates pathogenic processes of MS and, therefore, reduces disease severity and -burden. Not all approaches to treat additional immune-mediated disorders (e.g. Rasmussen Encephalitis and Neuromyelitis Optica) with natalizumab have been successful, but allowed researchers to gain additional insight into mechanisms of specific immune cell subsets' blood-brain-barrier migration in the human system. While the long-term efficacy and general tolerability of natalizumab in MS are clear, the over 400 cases of natalizumab-associated progressive multifocal leukoencephalopathy have been of great concern and methods of risk stratification in patients have become a major area of research. Modern risk stratification includes established factors such as treatment duration, previous immune-suppressive therapy, and anti-JC virus antibody seropositivity, but also experimental factors such as anti-JC virus antibody titers and levels of L-selectin. Today, anti-VLA-4 therapy is reserved for patients with highly active relapsing-remitting MS and patients are monitored closely for early signs of potential progressive multifocal leukoencephalopathy.
    International Immunology 10/2014;
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    ABSTRACT: The human immune system evolves continuously during development from the embryo into the adult, reflecting the ever-changing environment and demands of our body. This ability of our immune system to sense external cues and adapt as we develop is just as important in the early tolerogenic environment of the fetus, as it is in the constantly pathogen-challenged adult. Dendritic cells (DCs), the professional antigen-sensing and antigen-presenting components of the immune system, play a crucial role in this process where they act as sentinels, both initiating and regulating immune responses. Here we provide an overview of the human immune system in the developing fetus and the adult, with a focus on DC ontogeny and function during these discrete but intimately linked life stages.
    International Immunology 10/2014;
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    ABSTRACT: Despite extensive investigation over the past three decades, cancer immunotherapy has produced limited success, with few agents achieving approval by the Food and Drug Administration and even the most effective helping only a minority of patients, primarily with melanoma or renal cancer. In recent years immune checkpoints that maintain physiologic self-tolerance have been implicated in the downregulation of antitumor immunity. Efforts to restore latent antitumor immunity have focused on antibody-based interventions targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) on T lymphocytes, and its principal ligand (PD-L1) on tumor cells. Ipilimumab, an antibody targeting CTLA-4, appears to restore tumor immunity at the priming phase whereas anti-PD- 1/PD-L1 antibodies restore immune function in the tumor microenvironment. Although ipilimumab can produce durable long-term responses in patients with advanced melanoma, it is associated with significant immune-related toxicities. By contrast, antibodies targeting either PD-1 or PD-L1 have produced significant antitumor activity with considerably less toxicity. Activity was seen in patients with melanoma and renal cancer, as well as those with non-small cell lung, bladder and head and neck cancers, tumors not previously felt to be sensitive to immunotherapy. The tolerability of PD-1-pathway blockers and their unique mechanism of action have made them ideal backbones for combination regimen development. Combination approaches involving cytotoxic chemotherapy, anti-angiogenic agents, alternative immune-checkpoint inhibitors, immunostimulatory cytokines and cancer vaccines, are currently under clinical investigation. Current efforts focus on registration trials of single agents and combinations in various diseases and disease settings and identifying predictive biomarkers of response.
    International Immunology 10/2014;
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    ABSTRACT: Infection with certain pathogens induces a shift of the Th subset balance to a Th1 dominant state. This, in turn, results in the suppression of Th2 responses. We focused on the involvement of IRF-1 in the suppression of Th2 cells during Listeria infection. We found that the inhibition of IL-4 production by Th2 cells is mediated by a soluble factor (LmSN) produced by Listeria-infected APCs. The inhibition is not observed with T cells from Irf1 gene targeted mice. IRF-1 suppresses transcription of the Il4 gene in Th2 cells. Under the influence of the LmSN, IRF-1 binds to the 3'UTR region of the Il4 gene and down-regulates Il4 gene transcription. Finally, we identified IL-1α and IL-1β as the mediator of the LmSN activity. Signaling through IL-1R induces the stabilization and/or nuclear translocation of IRF-1. We propose that IRF-1 functions to induce the T cell subset shift via a novel mechanism. Under the influence of IL-1, IRF-1 translocates into the nucleus and acts on the 3'UTR region of the Il4 gene, thus inhibiting its transcription in Th2 cells. As a result, the immune system shifts predominantly to a Th1 response during Listeria-infection, resulting in effective protection of the host.
    International Immunology 10/2014;
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    ABSTRACT: M2 macrophages have been subdivided into subtypes such as IL-4-induced M2a and IL-10-induced M2c in vitro. Although it was reported that IL-10 stimulation leads to an increase in IL-4Rα, the effect of IL-4 and IL-10 in combination on macrophage subtype differentiation remains unclear. Thus, we sought to clarify whether IL-10 enhanced the M2 phenotype induced by IL-4. In this study, we showed that IL-10 enhanced IL-4Rα expression in M-CSF-induced bone marrow-derived macrophages (BMDM). Global gene expression analysis of M2 macrophages induced by IL-4, IL-10 or IL-4 + IL-10 showed that IL-10 enhanced gene expression of M2a markers induced by IL-4 in M-CSF-induced BMDM. Moreover, IL-4 and IL-10 synergistically induced CCL24 (Eotaxin-2) production. Enhanced CCL24 expression was also observed in GM-CSF-induced BMDM, and zymosan-elicited, thioglycolate-elicited and naive peritoneal macrophages. CCL24 is a CCR3 agonist and an eosinophil chemoattractant. In vitro, IL-4 + IL-10-stimulated macrophages produced a large amount of CCL24 and increased eosinophil migration which was inhibited by anti-CCL24 antibody. We also showed that IL-4 + IL-10-stimulated (but not IL-4 or IL-10 alone) macrophages transferred into the peritoneum of C57BL/6J mice increased eosinophil infiltration into the peritoneal cavity. These results demonstrate that IL-4 + IL-10-simulated macrophages have enhanced M2a macrophage-related gene expression, CCL24 production, and eosinophil infiltration-inducing activity, thereby suggesting their contribution to eosinophil-related diseases.
    International Immunology 09/2014;
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    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 diseases. To restrict NA-sensing in endolysosomes, TLR7/9 trafficking is tightly controlled by a multiple transmembrane protein Unc93B1. In contrast to TLR7/9 trafficking, little is known about a mechanism underlying NA transportation. We here show that Mucolipin 1 (Mcoln1), a member of the transient receptor potential (TRP) cation channel gene family, has an important role in ssRNA trafficking into lysosomes. Mcoln1(-/-) dendritic cells (DCs) showed impaired TLR7 responses to ssRNA. A mucolipin agonist specifically enhanced TLR7 responses to ssRNAs. The channel activity of Mcoln1 is activated by a phospholipid PtdIns(3,5)P2, which is generated by a class III lipid kinase PIKfyve. PIKfyve inhibitor completely inhibited TLR7 responses to ssRNA in DCs. Confocal analyses showed that ssRNA transportation to lysosomes in DCs was impaired by PIKfyve inhibitor as well as by the lack of Mcoln1. Transportation of TLR9 ligands was also impaired by PIKfyve inhibitor. These results demonstrate that the PtdIns(3,5)P2-Mcoln1 axis has an important role in ssRNA transportation into lysosomes in DCs.
    International Immunology 09/2014;
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    ABSTRACT: We previously generated a rat model that spontaneously developed small vessel vasculitis (SVV). In this study, a T cell clone reactive with rat vascular endothelial cells (REC) was established and named VASC-1. Intravenous injection of VASC-1 induced SVV in normal recipients. VASC-1 was a TCRαβ/CD3-positive CD4/CD8 double-negative T cell clone with expression of NKG2D. The cytokine mRNA profile under unstimulated condition was positive for IL-4 and IFN-γ but negative for IL-2 and IL-10. After interaction with REC, the mRNA expressions of IL-2, IL-5, and IL-6 were induced in VASC-1, which were inhibited by blocking of CD1d on the REC surface. Although the protein levels of these cytokines seemed to be lower than the detection limit in the culture medium, IFN-γ was detectable. The production of IFN-γ from the VASC-1 stimulated with LPS-pretreated REC was inhibited by the CD1d blockade on the REC. These findings indicated VASC-1 as an NKT cell clone. NKT cell pool includes two major subsets, namely type I and type II. Type I NKT cells are characterized by expression of semi-invariant TCRs and potential to bind to marine sponge-derived α-galactosylceramide (α-GalCer) loaded on CD1d; whereas, type II NKT cells do not manifest the characteristics. VASC-1 exhibited a usage of TCR other than the type I invariant TCR α chain and did not bind to α-GalCer-loaded CD1d; therefore, it was determined as a type II NKT cell clone. The collective evidence suggested that REC-reactive type II NKT cells could be involved in the pathogenesis of SVV in rats.
    International Immunology 09/2014;
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    ABSTRACT: Multi-agent chemotherapy is the standard treatment for most B cell malignancies. Since chemotherapy can be associated with significant toxicity and since relapses resistant to chemotherapy often develop, new therapies are needed. Blinatumomab (AMG 103 or MT103) is a late-stage candidate in clinical development, which belongs to a novel class of antibody constructs termed bi-specific T cell engager (BiTE(®)) antibodies. This antibody construct has dual specificity for CD19 and CD3 and can redirect polyclonal cytotoxic T lymphocytes toward the tumor. This review focuses on the pre-clinical and clinical development of blinatumomab as a powerful new tool in the treatment of B cell malignancies.
    International Immunology 09/2014;
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    ABSTRACT: Regulatory T cells (Tregs) play a critical role in the maintenance of immunological tolerance. The best characterized Tregs are those expressing the transcription factor Foxp3 and in vivo modulation of Foxp3 Tregs has been employed to study their role in immune homeostasis. Latency associated peptide (LAP) is a membrane bound TGF-β complex that has also been shown to play a role in Treg function and oral tolerance. We developed a novel anti-mouse LAP monoclonal antibody that allowed us to investigate the effect of targeting LAP in vivo on immune function and on anti-CD3 induced oral tolerance. We found that in vivo anti-LAP monoclonal antibody administration led to a decrease in the number of CD4+LAP+ Tregs in spleen and lymph nodes without affecting CD4+Foxp3+ Tregs. Spleen cells from anti-LAP injected mice proliferated more in vitro and produced increased amounts of IL-2, IL-17 and IFN-γ. Moreover, injection of anti-LAP antibody abrogated the protective effect of oral anti-CD3 on EAE Finally, in vivo anti-LAP administration prior to MOG immunization resulted in severe EAE in the absence of pertussis toxin, which is used for EAE induction. Our findings demonstrate the importance of CD4+LAP+ T cells in the control of immune homeostasis and autoimmunity and provides a new tool for the in vivo investigation of murine LAP+ Tregs on immune function.
    International Immunology 09/2014;
  • International Immunology 09/2014; 26(9):479-80.