International Immunology (INT IMMUNOL )

Publisher: Oxford University Press


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

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  • Website
    International Immunology website
  • Other titles
    International immunology online., International immunology
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  • Material type
    Periodical, Internet resource
  • Document type
    Journal / Magazine / Newspaper, Internet Resource

Publisher details

Oxford University Press

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    • 12 months embargo on science, technology, medicine articles
    • 2 years embargo on arts and humanities articles
    • Some titles may have different embargoes
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    • 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
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    • 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
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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Activation-induced cytidine deaminase (AID) is essential to class switch recombination (CSR) and somatic hypermutation (SHM). Uracil DNA glycosylase (UNG), a member of the base excision repair (BER) complex, is required for CSR. Role of UNG in CSR and SHM is extremely controversial. AID deficient mice abolish both CSR and SHM, while UNG deficient mice drastically reduced CSR but augment SHM raising a possibility of differential functions of UNG in CSR and SHM. Interestingly, UNG has been associated with a CSR specific repair adapter protein Brd4, which interacts with acetyl histone 4, γH2AX and 53BP1 to promote nonhomologous end joining (NHEJ) during CSR. A non-canonical scaffold function of UNG, but not the catalytic activity, attributed to the recruitment of essential repair proteins associated with the error-free repair during SHM, and the end-joining during CSR.
    International Immunology 07/2014;
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    ABSTRACT: Red algae sulfated polysaccharides - carrageenans - are widely used in the medical and food fields owing to their physico-chemical properties and different biological activity. Such polyionic polysaccharides as carrageenans are capable of multipoint interaction with ummunocompetent cell surface. Modulation of the ability of carrageenans with different structural type isolated from the red seaweeds collected from Pacific coast to activate in vitro the production of TNFa, IL6 and IL10 was investigated. The results have showed that all the investigated carrageenan samples demonstrated the cytokine-inducing activity stimulating their synthesis depending on the polysaccharide concentration and structure. The additive "Carrageenan DV" influence on the patient group with diabetes mellitus 2 type moderate severity has been investigated. Both the relative (p , 0.01) and absolute (p , 0.05) increase of CD4+ lymphocyte amount has been observed after additive application. The CD8+ lymphocyte level has slight changed. It has also been observed the tendency to lowering the immunoglobulins: IgG, IgM (p , 0.01), IgA, but the IgA concentration has been still elevated. Carrageenan increases the phagocytosis which is suggested with advance the phagocytic indices: phagocytic frequency (p , 0.01), phagocytic index and complete phagocytosis index (p , 0.05). The proinflammatory cytokine level reduction occurred by additive effect, the IL1b and IL6 concentration continued to be heightened, the INFg production was significantly activated (p , 0.05), but at the same time the IL4 synthesis increased (p , 0.01) keeping being normally. Hence additive "Carrageenan DV" expresses the positive influence on the nonspecific immune system - phagocytosis - and the correcting action on Th-1 cells owing to stimulating INFg (p , 0.05).
    International Immunology 08/2010; 22(1):i161.
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    ABSTRACT: Activation of T cells requires co-stimulation, in addition to signals through the antigen-receptor complex. Antigen encounter without adequate co-stimulation results in T-cell desensitization or anergy, a mechanism of peripheral tolerance and an apparent obstacle to cancer immunotherapy. One important co-stimulatory pathway involves CD28 engagement by CD80 or CD86. However, other ligand-receptor pairs can also provide co-stimulation and may have important functions modulating the immune response. Previous reports indicated that co-stimulation using 4-1BB ligand (4-1BBL) or agonistic anti-4-1BB antibodies could prolong T-cell responses, avoid activation-induced cell death and promote anti-tumour responses in mice. To further investigate the potential for cancer immunotherapy, we studied the effects of CD80/CD86 and 4-1BBL in repeated stimulation of human T cells and asked whether 4-1BBL might be capable of reversing anergy. We expressed CD80, CD86 and 4-1BBL in A549 lung carcinoma cells using adenovirus vectors and co-cultured these with human T cells stimulated with anti-CD3 antibody. Proliferation co-stimulated by CD80 or CD86 was transient; however, 4-1BBL-co-stimulated cultures continued to proliferate for up to 5 weeks, with repeated stimulation. Combined co-stimulation with CD80/CD86 and 4-1BBL also allowed continuous proliferation at a faster rate than either signal alone. Co-stimulation with 4-1BBL did not suppress expression of the inducible, inhibitory CD80/CD86R, CTLA-4. Significantly, we show that T cells that had become non-responsive to anti-CD3, either alone or together with CD80/CD86 co-stimulation, and thus were anergic, could be reactivated to proliferate when costimulated with 4-1BBL, either alone or combined with CD80/CD86.
    International Immunology 01/2008; 19(12):1383-94.
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    ABSTRACT: TLR3 plays an important role in the activation of different cell types of the innate immune system. Previous studies indicated that human NK cells express TLR3 and that, upon stimulation by polyinosinic-polycytidylic acid [poly (I:C)], they release cytokines and up-regulate cytotoxicity. Here we show that NK cells display heterogeneous levels of TLR3 mRNA transcript. Analysis of NK cell clones did not reveal significant correlation between the levels of TLR3 mRNA transcripts and the expression of different surface NK receptors including killer Ig-like receptor and NKG2A. On the other hand, the level of TLR3 mRNA transcript detected in given clones correlated with the ability of these clones to respond to poly (I:C). Thus, clones displaying higher TLR3 mRNA transcripts were characterized by higher cytokine production and cytotoxicity. Moreover, the increased cytolytic activity induced by treatment with poly (I:C) does not depend on increment of the expression of activating NK receptors and co-receptors, adhesion molecules or perforin/granzyme, but correlates with higher cell responsiveness to NKp46 ligation. Remarkably, in the presence of poly (I:C), even NKp46(dull) NK cell clones become cytolytic when characterized by high levels of TLR3 transcript. Thus, our present study provides an useful tool for both a quantitative and qualitative analysis of TLR3 in NK cells and contributes to explain the heterogeneous responsiveness to poly (I:C) of NK cells derived from different individuals.
    International Immunology 01/2008; 19(12):1341-8.
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    ABSTRACT: Although the recruitment of macrophages to the lung is a central feature of airway inflammation, its function in ongoing T(h)2 cell-mediated eosinophilic airway inflammation remains controversial. Here, we have demonstrated that the allergen-induced CD11b(+) CD11c(int) macrophage expressing CC chemokine receptor 3 (CCR3) in the lung performs a crucial function in the induction of eosinophilic asthma in a murine model. In the lungs of normal mice, residential cells evidencing high granularity phenotypically evidenced CD11b(int) CD11c(+) or CD11b(+) CD11c(int) cells, appearing at a 2:1 ratio. After allergen challenge, however, this reverses dramatically, up to a ratio of one to six. Approximately 91% of increased CD11b(+) CD11c(int) cells evidenced the expression of the CCR3 eotaxin receptor, but not other chemokine receptors, such as CCR5 and CXCR4. Interestingly, the CD11b(+) CD11c(int) cells purified from the lungs of OVA (ovalbumin)-sensitized and challenged mice evidenced higher antigen-presenting activity than was observed in CD11b(int) CD11c(+) cells. In order to investigate the in vivo function of CD11b(+) CD11c(int) cells, the cells were isolated from the lungs of OVA-sensitized and challenged mice and then adoptively transferred prior to the allergen challenge of normal mice. In the CD11b(+) CD11c(int)-transferred mice airway hyperresponsiveness, eosinophilic inflammation in the lung and T(h)2 cytokine secretion in the bronchoalveolar lavage fluids were significantly enhanced as the result of OVA challenge, as compared with the mice that received OVA-primed CD90(+) T cells or CD11b(int) CD11c(+) cells. These findings show that CD11b(+) CD11c(int) macrophages expressing CCR3 as key pro-inflammatory cells are both necessary and sufficient for allergen-specific T cell stimulation during ongoing eosinophilic airway inflammation.
    International Immunology 01/2008; 19(12):1371-81.
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    ABSTRACT: IL-7 receptor alpha (CD127) signaling is essential for T-cell development and regulation of naive and memory T-cell homeostasis. Fewer CD8(+) T cells from HIV-infected patients express CD127 compared with healthy individuals, suggesting that specific host and/or viral factors regulate IL-7 receptor expression. Factors relevant to HIV infection that could potentially decrease CD127 expression on human CD8(+) T cells and the mechanisms by which this occurs were therefore evaluated. IL-7, but not HIV gp120, IL-1-beta, IL-6, IL-10, IL-13, transforming growth factor-beta or tumor necrosis factor-alpha, reduced CD127-surface expression and did so without altering CD127 mRNA expression. Furthermore, IL-7 did not increase the amount of cytoplasmic CD127 in CD8(+) T cells. Interestingly, IL-7 induced the shedding of CD127 from CD8(+) T cells, suggesting a mechanism that may contribute to the increased concentration of CD127 in the plasma of HIV(+) individuals, a novel finding reported here. Naive CD8(+) T cells are more sensitive to IL-7 that mediated the down-regulation of CD127, suggesting that these effects may have particular significance early in T-cell life cycle. Since CD127 down-regulation may be an important contributor to HIV-associated T-cell dysfunction, determining the mechanism thereof may prove to be of considerable significance.
    International Immunology 01/2008; 19(12):1329-39.
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    ABSTRACT: The B cell antigen receptor (BCR) delivers antigen to the endocytic compartment and transduces signals that regulate the stability of the receptor complex. Previous studies showed that BCR-mediated signal transduction dissociates micro-heavy chain (microm) from Ig-alpha/Ig-beta, facilitating the delivery of antigen to clathrin-coated vesicles (CCVs). Herein, we demonstrate that the dissociation of Ig-alpha/Ig-beta from microm requires tyrosine-587 of the microm transmembrane domain. Receptors expressing a mutation at tyrosine-587 (Y587F) transduced signals that were comparable to wild type, yet they failed to dissociate microm from Ig-alpha/Ig-beta. Further, receptors harboring the Y587F mutation failed to associate with CCVs, resulting in diminished antigen in the lysosome-associated membrane protein-1 (LAMP-1(+)) compartment and severely impaired antigen presentation, indicating that endocytosis through CCVs is required for antigen presentation. Thus, the transmembrane tyrosine of mum mediates destabilization of the BCR complex, facilitating antigen processing by promoting the association of antigen with CCVs.
    International Immunology 01/2008; 19(12):1403-12.
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    ABSTRACT: Although a severe shortage of organs in transplantation can be overcome by using xenotransplantation of porcine donor organs, profound immune rejection to xenogeneic antigens remains a main obstacle. To elucidate the role of hydrogen peroxide (H(2)O(2)) on xenogeneic immune responses, we investigated its effects on porcine aortic endothelial cells (PAECs). We found that H(2)O(2) can specifically induce vascular cell adhesion molecule-1 (VCAM-1) expression on PAECs, but little on human umbilical vein endothelial cells (HUVECs) and aortic endothelial cells (HAECs). Furthermore, we further confirmed that H(2)O(2) induces activation of NFkappaB in PAECs, but not in HAECs. Interestingly, cell adhesion assay showed that U937, human promonocytic leukocyte, can adhere to PAECs in an H(2)O(2)-dependent manner and by using a neutralizing assay with anti-VCAM-1-specific antibodies, we also found that the interaction is mediated primarily by VCAM-1. Finally, we also demonstrated that up-regulation of VCAM-1 expression on PAECs by reactive oxygen species-producing HL-60, human leukemic neutrophil cells, could be significantly diminished by over-expressing an H(2)O(2)-removing catalase. In summary, our results suggest that NFkappaB-dependent porcine VCAM-1 expression by H(2)O(2) may promote interaction of human leukocyte to PAECs, and thus may play an important role on inducing xenogeneic immune responses.
    International Immunology 01/2008; 19(12):1349-59.
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    ABSTRACT: The adaptor protein CD2-binding protein 2 (CD2BP2) confers binding to proline-rich sequences (PRS) via its GYF domain. In addition to the cytoplasmic domain of CD2, several other proteins were identified as interaction partners of CD2BP2, but the in vivo significance of these findings is unclear. We now show that CD2BP2's nuclear localization is not changed when CD2 and CD2BP2 are co-expressed in HeLa cells, indicating that other PRS compete effectively for CD2BP2 binding in the nucleus. Since the CD2BP2-binding motifs of CD2 are known to be involved in cytokine signaling, we tested the effect of CD2BP2 knockdown in PBMCs on the expression of T-cell cytokines. No major difference in cytokine expression can be observed for primary cells transfected with CD2BP2-specific small interfering RNA. We conclude that CD2 signaling is at least partially independent of its in vitro binding partner CD2BP2.
    International Immunology 12/2007; 19(11):1313-8.
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    ABSTRACT: The CC chemokine receptor 7 (CCR7) and its two ligands, CCL21 and CCL19, play an important role in migration of immune cells to lymphoid tissue. To analyze the function of CCR7 in T cell immunity to infectious agents in vivo, transgenic (tg) mice expressing CCL21 in an ubiquitous fashion were generated. These mice contained high amounts of CCL21 in the serum ( approximately 0.3 microg/ml that resulted in CCR7 down-regulation and in a strongly impaired migration of T cells toward CCL21 in vitro. Lymph nodes in CCL21-tg mice were reduced in size but with intact microanatomy and normal distribution of T and B cells. CCL21-tg mice showed a significantly decreased CD8 T cell response to lymphocytic choriomeningitis virus after footpad infection, whereas the response after systemic infection was not altered. Likewise, the CD4 T cell response to footpad infection with Leishmania major was considerably lowered and CCL21-tg mice failed to clear parasites from infected skin. Taken together, these data demonstrate the importance of CCR7 in mediating T cell immunity to viral and parasitic pathogens after local infection.
    International Immunology 12/2007; 19(11):1281-9.
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    ABSTRACT: Reactivation of latent human cytomegalovirus following allogeneic transplantation is a major cause of morbidity and mortality and predisposes to severe complications. Thymosin alpha1 (Talpha1), a naturally occurring thymic peptide, is approved for treatment of some viral infections and as an immune adjuvant. Talpha1 successfully primed dendritic cells (DCs) for anti-microbial T helper type 1 resistance through Toll-like receptor (TLR) 9 signaling. We sought to determine here whether Talpha1 could play a role in murine cytomegalovirus infection (MCMV). To this purpose, susceptible, resistant and TLR-deficient mice were infected with MCMV, treated with Talpha1 and assessed for protection in term of microbiological and immunological parameters. Talpha1 protected susceptible and resistant mice from MCMV infection. The anti-viral effect of Talpha1 occurred through the activation of plasmacytoid DCs via the TLR9/myeloid differentiation primary response gene 88-dependent viral recognition sensing, leading to the activation of IFN regulatory factor 7 and the promotion of the IFN-alpha/IFN-gamma-dependent effector pathway.
    International Immunology 12/2007; 19(11):1261-70.