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  • 1
    Electronic Resource
    Electronic Resource
    Liver Metastasis of Cancer Facilitated by Chemokine Receptor CCR6 (2003)
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 57 (2003), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: When injected subcutaneously, mouse plasmacytoma (MOPC315) grew rapidly in situ, and metastatic cells became detectable first in the lymph nodes (LNs) and bone marrow, and later in the liver and lungs. We studied MOPC315 cell migration by tracking metastatic cells labelled with green fluorescent protein (GFP). We measured the levels of their chemokine receptor mRNA (by semiquantitative and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), because chemokines can regulate organ predilection of metastasis. Freshly sorted metastatic cells and tumour cell lines derived from the liver of BALB/c mice overexpressed functional CCR6 and CCR7 molecules compared with primary tumour. Preincubation with the CCR6 ligand (CCL20) induced liver-sorted tumour cells to preferentially colonize the liver, demonstrating an association between liver metastasis and CCR6 expression in the mouse. Because the liver is a common site for metastasis, second only to draining LNs, we wished to ascertain whether this finding could be generalized, i.e. whether other cancers can use the similar mechanism of metastasis to the liver, and whether it holds true for humans. We found that CCR6 is overexpressed in small liver metastases of colon, thyroid and ovarian carcinomas compared with normal liver. Because human liver constitutively expresses CCL20, it could attract and select CCR6+ cancer cells. We suggest that chemotaxis via CCR6 might be a common mechanism by which malignant cancers metastasize to the liver. As metastasis in patients with cancer poses the biggest peril for survival, inhibition of CCR6 signalling, either during or after medical or surgical treatment, might be useful in preventing liver metastasis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.2003.01263.x
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  • 2
    Electronic Resource
    Electronic Resource
    Idiotype-Specific, Major Histocompatibility Complex Restricted T Cells are of both Th1 and Th2 Type (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 33 (1991), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The lymphokine secretion patterns of seven independent 91–101.γ2315/1-Ed specific. CD4+ T-cell clones have been investigated. Six of the clones are of the Thl type as they secrete IL2 and IFNγ, but not IL4. Some of these SIX Thi clones produce TNF α/β, and some produce minor amounts of IL5 and IL6. One clone is of the Th2 type as it produces 1L4, IL5. and large amounts of 1L6. but not IL2, IFNγ or TNF. The Thl, Th2 classification does not have any stringent relationship to immunization protocol, fine specificity and Vα/Vβ gene segment utilization. The immunoregulatory significance of our findings for Id/MHC-dependent T B cell interaction is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1991.tb02537.x
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  • 3
    Electronic Resource
    Electronic Resource
    H-2-Linked Ir Genes Have a Striking Influence on the Immunogenicity of Idiotopes of Myeloma Protein 315 for T Helper Cells (1985)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 21 (1985), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: H-2-linked immune response (Ir) genes control T helper cells (Th) that recognize idiotopes of the V domains of myeloma protein 315 as carriers; Th recognition was detected by augmentation of antibody responses of hapten (4-hydroxy-3-iodo-5-nitrophenylacetyl (NIP))-primed B cells boosted with NIP conjugated to Fab315. The present study indicates that the responder k allele of the Ir VH315 gene maps to the I-A subregion of H-2. A responder s allele of the Ir Vλ2315 gene on an A-strain background was identified, which also most likely maps to I-A. Although the d allele of the Ir Vλ2315 gene is a responder allele on DBA/2 background, the D2.GD strain (with I-region haplotype AdBbJbEbCb) was non-responder to Vλ2315, suggesting either that the responder d allele maps to I-E or that the b allele of a second Ir Vλ2315 gene located to the right of I-A exerts a strong suppressive influence. The H-2b haplotype conferred non-responsiveness to VH315, Vλ2315, and Fv315.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1985.tb01418.x
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  • 4
    Electronic Resource
    Electronic Resource
    Anti-Class II Antibodies, but not Cytotoxic T-Lymphocyte Antigen 4–Immunoglobulin Hybrid Molecules, Prevent Rejection of Major Histocompatibility Complex Class II-Negative Myeloma in T-Cell Receptor-Transgenic Mice (2004)
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Scandinavian journal of immunology 60 (2004), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have previously shown that tumour-specific CD4+ T cells protect against subcutaneous injections of major histocompatibility complex (MHC) class II-negative MOPC315 myeloma cells. Here, we have interfered with the immunologic events that lead to successful rejection of MOPC315 challenges in T-cell receptor (TCR)-transgenic mice. The CD4+ T cells have a transgene-encoded TCR specific for a MOPC315 V-region idiotypic (Id) peptide presented on the MHC class II molecule Ed. A side-by-side comparison indicated that DNA-recombination-deficient TCR-transgenic mice were better protected against MOPC315 tumour development than recombination-sufficient counterparts, suggesting that B cells or endogenous TCR chains might facilitate tumour progression in this model. Intraperitoneal injections of Ed-specific antibodies over a period of initial 24 days, abrogated protection against tumours in both strains of mice. By contrast, injections of anticostimulatory molecules (cytotoxic T-lymphocyte antigen 4–immunoglobulin hybrid molecules) had no effect. The findings demonstrate that tumour rejection depends on the presence of MHC class II molecules, despite the fact that MOPC315 tumour cells themselves do not express them. The results are consistent with the idea that secreted myeloma protein is processed and presented by class II+ antigen-presenting cells to Id-specific naïve CD4+ T cells that become activated and kill the myeloma cells by a bystander mechanism. While Id presentation on class II molecules is absolutely required for tumour rejection, costimulatory CD80/CD86 molecules might be dispensible in this process.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0300-9475.2004.01435.x
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  • 5
    Electronic Resource
    Electronic Resource
    Tumour Necrosis Factor Receptor Superfamily Member 6 Gene Mutation Detection by Denaturing High-Performance Liquid Chromatography (2004)
    Oxford, UK; Malden, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 59 (2004), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Denaturing high-performance liquid chromatography (DHPLC) was evaluated as a tool for diagnostic screening of polymorphisms in the tumour necrosis factor receptor superfamily member 6 (TNFRSF6) also known as CD95, Apo-1 or Fas gene. Exons 1–9 of the TNFRSF6 gene were amplified from genomic DNA of 38 individuals, of which three were known to carry mutations in the TNFRSF6 gene. The TNFRSF6 gene amplicons were analysed for heterozygosity by DHPLC. Samples that displayed heterozygous variation by DHPLC were further analysed by sequencing. Comparison of DHPLC analysis with sequencing results showed an overall 100% concordance for samples in which heterozygosity was detected by DHPLC. Importantly, DHPLC was in all cases able to demonstrate the presence or absence of mutations in exon 9 encoding the death domain of the TNFRSF6 gene, which have been implied as the most frequent genetic cause of autoimmune lymphoproliferative syndrome. Comparison of DHPLC analysis with sequencing results showed an overall 100% concordance for samples in which heterozygosity was detected by DHPLC. In conclusion, DHPLC is a suitable method for the detection of genetic variation in the TNFRSF6 gene.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0300-9475.2004.01422.x
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  • 6
    Electronic Resource
    Electronic Resource
    T-Cell Receptor Alpha Haplotype influences Vα Epitope Expression on both Cortisone-Resistant Thymocytes and Lymph Node T Cells (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 37 (1993), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have previously described a mouse strain congenic for the T-cell receptor alpha chain locus (Tcra). The strain, B10.D2.C-Tcraa/Bo, carries the Tcraa haplotype of BALB/c instead of the Tcraa haplotype normally found in B10.D2. By comparing B10.D2.C-Tcraa and B10.D2 mice, we now show that the Tcra haplotype influences the frequencies of Vα8 epitope expression on T cells detected by the novel B21.14 monoclonal antibody (MoAb). This finding agrees well with our previous observation that Tcra haplotype influences the frequencies of expression of two other Vα8 epitopes, detected by the KT50 and KT65 MoAbs. The specificities of the three Vα8-specific MoAbs were compared by scatter diagram analysis of staining frequencies obtained in individual mice. The B21.14 and KT50 MoAbs appear to have very similar specificities; these two MoAbs stain slightly more αβ T cells than the KT65 MoAb. Investigations with another novel MoAb, the Vα2-specific B20.1, revealed that the Tcra haplotype also influences the frequency of Vα2 epitope expression. The effect of the Tcra haplotype on Vα2 epitope expression was evident not only among lymph node T cells but also among mature, cortisone-resistant thymocytes. Thus, the influence of the Tcra haplotype is imprinted already in the thymus. The most likely explanations for Tcra haplotype dependency of Vα epitope expression are differing numbers of Vα-gene segment subfamily members and/or allelic polymorphism. The significance of Tcra haplotype-dependent Vα epitope expression is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1993.tb01685.x
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  • 7
    Electronic Resource
    Electronic Resource
    Monoclonal Antibodies Specific for Variable and Constant Domains of Murine λ Chains (1989)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 29 (1989), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Rat monoclonal antibodies directed against the BALB/c myeloma protein M315 (α,λ2) are described. 9A8 (IgG1) binds the V domain of λ2 and cross-reacts with λ1 and λ3 chains. 2B6 (IgG2a) is directed to the C domain of λ2 and cross-reacts λ3. The antibodies bind isolated chains as well us complete immunoglobulins. The monoclonals detect soluble immunoglobulin (radioimmunoassay), immunoglobulin immobilized on polystyrene (enzyme-linked immunosorbent assay), immunoglobulin bound to nitrocellulose (immunoblotting), and surface immunoglobulin intercalated in cell membranes (immunofluorescence). The antibodies are easily purified on protein G immunosorbents and may be biotinylated or conjugated with fluorescein isothiocyanate without loss of capacity to bind. In addition to the anti-λ antibodies, a Cα2/Cα3-specific monoclonal antibody, 8D2 (IgG2a) is described.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1989.tb01125.x
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  • 8
    Electronic Resource
    Electronic Resource
    Antibody Responses to λ1J558 and λ2315 Light Chains (1984)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 20 (1984), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Specificity of BALB/c antibody responses to A chains of isologous myeloma proteins 315 and J558 was explored by enzyme-linked immunosorbent assay. A-chain binding antibodies were not detected when immunizing with assembled (H + L) myeloma proteins. However, relatively high titred IgG antibodies were elicited by free λ2315 immunization. Antibodies were directed to ‘hidden’ determinants since binding was abrogated upon H + L assembly of chains. At least a portion of antibodies bound antigenic determinants in the variable region and cross-reacted with λl land λ3 chains. Free λ11558 immunization induced low-titred, predominantly IgM antibodies that also only reacted with ‘hidden’ determinants. These determinants were most probably located in the constant (C) region and no cross-reaction to λ2 or λ3 was observed. An artefact of technical importance was noted: myeloma proteins exposed ‘hidden’ determinants on their A chains when coated directly to polystyrene walls. This ariefactual exposition was lost when anti C-region antibody spacer molecules were inserted between the wall and the myeloma proteins. Antibody and T helper cell (Th) responses to free λ2315 covaried significantly in various strains while antibody and Th responses to free λ11558 did not. In some strains, weak antibody responses were detected without detectable Th.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1984.tb01020.x
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  • 9
    Electronic Resource
    Electronic Resource
    Preferential Positive Selection of T Lymphocytes which Express Two Different TCRα Chains, an Endogenous and a Transgenic (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 42 (1995), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A hallmark of positive selection in T-cell receptor (TCR)-transgenic mice is a strong skewing towards the CD4+ or the CD8+ subset, depending on the class II or I restriction of the TCR, respectively. However, previous experiments in TCR transgenic mice specific for an Ig light chain (λ2315)/I-Ed class II molecule did not fit into this scheme because the authors observed an anomalous skewing towards CD8. In this paper, the authors show that endogenous TCRα chains are expressed on 〉 90% of CD4+ and CDS+ cells in this particular transgenic strain, even on a selecting H-2d haplotype. Endogenous TCRQ chains are first detected when double-positive thymocytes down-regulate either CD4 or CD8. Endogenous Vα seems to influence generation of T-cell subsets because CD4+ and CD8+ cells express different frequencies of endogenous Vα2 and Vα8. In the absence of endogenous TCRα chains in recombination-deficient TCR-transgenic severe combined immunodeficiency (SCID) mice, a strong skewing towards CD4+ T cells is seen, but such mice are severely T-cell deficient. As an explanation for these results, the authors suggest that the transgenic TCR has a too low affinity for efficient positive selection, therefore, TCRa gene rearrangements proceed. Endogenous TCRa paired with transgenic TCRβ could bind to class I or class II molecules, enhance positive selection and thereby production of CD4+ or CD8+ cells. Most of the ‘mismatched’ CD8+ cells are λ2315-specific and I-Ed class II restricted, and may function as idiotype-specific suppressors of B cells. These results may help explain the origin of dual TCRα T cells. Furthermore, the authors suggest that T cells ‘mismatched’ for co-receptor/TCR MHC-specificity may be enriched among dual TCRa T cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1995.tb03708.x
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  • 10
    Electronic Resource
    Electronic Resource
    Anti-Tumour Activity of Idiotype-Specific, MHC-Restricted Th1 and Th2 Clones In Vitro and In Vivo (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 37 (1993), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Idiotypes (Id) can serve as individual markers on B cells; therefore, cytotoxic Id-specific T cells may play a significant role in immunological surveillance of Id+ B-cell tumours. We have investigated the anti tumour activity of CD4+ BALB/c Thl and Th2 clones which recognize a processed Id of the syngeneic λ2315 L chain in the context of the class II MHC molecule I-Ed. Id-specific T cells and A 20/46 B lymphoma cells transfected with the λ2315 gene were injected s.c. into the same site of BALB/c mice (Winn assay). The results show that both Th l and Th2 clones can protect against tumour development. The protection was Id-specific because T cells did not influence tumour development by an A20/46 B lymphoma cell line transfected with the pSV2neo expression vector alone. In vitro studies showed that the Th1 clones were cytotoxic to λ2315 -transfected B lymphoma cells; by contrast, the Th2 clone was not cytotoxic in 5lCr-release assay even though the Th2 cells inhibited the growth of λ2315 B lymphoma cells. The anti lympboma properties of both the Thl and Th2 clones appear to involve as yet undefined cytotoxic and growth inhibiting molecules.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1993.tb01668.x
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