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.

  • Impact factor
    Show impact factor history
    Impact factor
  • 5-year impact
  • Cited half-life
  • Immediacy index
  • Eigenfactor
  • Article influence
  • Website
    International Immunology website
  • Other titles
    International immunology online., International immunology
  • ISSN
  • OCLC
  • 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

  • [Show abstract] [Hide abstract]
    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;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The immune system maintains homeostasis by recognizing and responding to cell death caused by various stresses. The immune response is considered to be elicited by "danger signals" released from necrotic cells. However, the identity of the danger signals remains elusive. In this study, we focused on the expression of chemokines by macrophages stimulated with necrotic cells. In mouse bone marrow-derived macrophages, the chemokine monocyte chemoattractant protein (MCP)-3 was induced at both the mRNA and protein levels in response to heat-killed murine cells. The induction of MCP-3 was also observed in MyD88-deficient macrophages, indicating that Toll-like receptors and the IL-1 receptor are not involved in this response. Consistent with this observation, the activation of NF-κB was not detected in RAW264.7 macrophages stimulated with necrotic cells. Treatments with proteinase K, DNase I, or RNase A did not affect the stimulating activity of necrotic cells. In contrast, treatment with apyrase, which removes phosphates from nucleoside tri-and diphosphates, abolished the inducing activity. Purified UDP at 30 μM concentration elicited similar induction of MCP-3 in RAW264.7 macrophages. siRNA-mediated knockdown of the UDP receptor P2Y6 in RAW264.7 cells significantly reduced the induction of MCP-3 in response to necrotic cells, but not its induction by lipopolysaccharide. Furthermore, ectopic expression of the P2Y6 receptor in HEK293 cells conferred responsiveness to necrotic cells. These results suggest that UDP released by necrotic cells plays a critical role as an endogenous danger signal and that P2Y6 is required for the induction of MCP-3 in response to necrotic cells.
    International Immunology 08/2014;
  • [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;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bone remodeling and hematopoiesis are interrelated and bone marrow macrophages are considered to be important for both bone remodeling and maintenance of the hematopoietic niche. We found that NF-ĸB Rela-deficient chimeric mice, generated by transplanting Rela(-/-) fetal liver cells into lethally irradiated hosts, developed severe osteopenia, reduced lymphopoiesis, and enhanced mobilization of hematopoietic stem and progenitor cells when bone marrow cells were completely substituted by Rela-deficient cells. Rela(-/-) hematopoietic stem cells from fetal liver had normal hematopoietic ability, but those harvested from the bone marrow of osteopenic Rela(-/-) chimeric mice had reduced repopulation ability, indicating impairment of the microenvironment for the hematopoietic niche. Osteopenia in Rela(-/-) chimeric mice was due to reduced bone formation, even though osteoblasts differentiated from host cells. This finding indicates impaired functional coupling between osteoblasts and hematopoietic stem cell-derived cells. Rela-deficient bone marrow macrophages exhibited an aberrant inflammatory phenotype, and transplantation with wild-type F4/80(+) bone marrow macrophages recovered bone formation and ameliorated lymphopoiesis in Rela(-/-) chimeric mice. Therefore, RELA in F4/80(+) macrophages is important both for bone homeostasis and for maintaining the hematopoietic niche after lethal irradiation and hematopoietic stem cell transplantation.
    International Immunology 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The natural killer group 2 membrane D (NKG2D) receptor is an NK-activating receptor that plays an important role in host defense against tumors and viral infections. Although the marmoset is an important and reliable animal model, especially for the study of human-specific viral infections, functional characterization of NKG2D on marmoset NK cells has not previously been conducted. In the present study, we investigated a subpopulation of marmoset NK cells that express NKG2D and exhibit cytolytic potential. Based on their CD16 and CD56 expression patterns, marmoset NK cells can be classified into three subpopulations: CD16(+)CD56(-), CD16(-)CD56(+), and CD16(-)CD56(-) cells. NKG2D expression on marmoset CD16(+)CD56(-) and CD16(-)CD56(+) splenocytes was confirmed using an NKG2D ligand comprised of an MHC class I chain-related molecule A (MICA)-Fc fusion protein. When marmoset splenocytes were cultured with IL-2 for 4 days, NKG2D expression was retained on CD16(+)CD56(-) and CD16(-)CD56(+). In addition, CD16(+)CD56(+) cells within the marmoset NK population appeared which expressed NKG2D after IL-2 stimulation. IL-2-activated marmoset NK cells showed strong cytolytic activity against K562 and MICA stably-expressing target cells. Further, the cytolytic activity of marmoset splenocytes was significantly reduced after addition of MICA-Fc fusion protein. Thus NKG2D functions as an activating receptor on marmoset NK cells that possesses cytotoxic potential, and phenotypic profiles of marmoset NK cell subpopulations are similar to that seen in humans.
    International Immunology 05/2014;
  • International Immunology 08/2010; 22(9):775-782.
  • [Show abstract] [Hide abstract]
    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.
  • International Immunology 11/2008; 20(12):1565-1573.
  • [Show abstract] [Hide abstract]
    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.
  • Source
    [Show abstract] [Hide abstract]
    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.
  • [Show abstract] [Hide abstract]
    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.
  • [Show abstract] [Hide abstract]
    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.