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  • The American Association of Immunologists  (5)
  • 1
    Online Resource
    Online Resource
    Characterization of lidocaine-specific T cells.
    The American Association of Immunologists ; 1997
    In:  The Journal of Immunology Vol. 158, No. 3 ( 1997-02-01), p. 1139-1148
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 158, No. 3 ( 1997-02-01), p. 1139-1148
    Abstract: To investigate the cellular immune response to the drug lidocaine, we generated T cell lines and clones from the peripheral blood of four patients with proven allergy to lidocaine. The patients had contact dermatitis after topical application of lidocaine, and local swelling or generalized erythema exudativum multiforme after submucosal/subcutaneous injection of lidocaine. Two of three lidocaine-specific T cell lines were oligoclonal and one even became monoclonal, while the simultaneously analyzed immune response to tetanus toxoid was polyclonal. The lidocaine-specific T cell lines cross-reacted to mepivacaine, but not to other local anesthetics (bupivacaine, procaine, oxybuprocaine, and tetracaine). The majority of reactive T cells belonged to the CD4 cell lineage and were MHC class II restricted, but cloning also revealed some MHC class I-restricted CD8+ clones. A total of 2 of 56 lidocaine-specific T cell clones were CD4-CD8- and expressed TCR-gammadelta. The majority of 13 analyzed CD4 clones produced a rather polarized cytokine pattern, with a dominance of Th2-like cytokines showing a high IL-5 production. In addition, three CD4+ and all CD8+ (n = 7) clones secreted high IFN-gamma and low levels of IL-5/IL-4 (Th1-like). The data illustrate that a drug that sensitizes via the skin elicits a heterogeneous T cell response. The high IL-5 production and the participation of specific CD4+CD8+ and even gammadelta+ T cells appear to be distinguishing features of this hapten-specific immune response.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.158.3.1139
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 1997
    detail.hit.zdb_id: 1475085-5
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  • 2
    Online Resource
    Online Resource
    Activation of drug-specific CD4+ and CD8+ T cells in individuals allergic to sulfonamides, phenytoin, and carbamazepine.
    The American Association of Immunologists ; 1995
    In:  The Journal of Immunology Vol. 155, No. 1 ( 1995-07-01), p. 462-472
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 155, No. 1 ( 1995-07-01), p. 462-472
    Abstract: To investigate how T cells are involved in hypersensitivity reactions to drugs that become immunogenic after metabolization, e.g., sulfonamides and antiepileptics, we analyzed in vitro the drug-induced activation of CD4+ and CD8+ T cell subsets, cytokine secretion, TCR V beta distribution, and proliferation of T cells from four drug-allergic individuals. In addition, the activation parameters CD25 and HLA-DR were analyzed in vivo on CD4+ and CD8+ T cells from five patients with acute drug allergies, some of them with anticonvulsant hypersensitivity syndrome with hepatitis. Our results show that, in vitro, drug-induced proliferation of PBMC from patients with allergy to sulfamethoxazole, phenytoin, or carbamazepine was specific and dose dependent. CD4+ as well as CD8+ T cells expressed elevated levels of CD25 and HLA-DR molecules after drug stimulation. Drug-activated lymphocytes secreted high amounts of IL-5 and normal or low levels of IL-2, IFN-gamma, IL-4, and TNF-alpha. An enhanced expansion of TCR V beta 17+ T cells 9 days after in vitro stimulation with sulfamethoxazole was observed in one patient with sulfamethoxazole allergy. The drug specificity of the in vitro-activated T cells was confirmed by generation of different sulfamethoxazole specific T cell lines and CD4+ and CD8+ T cell clones. T cell analysis of patients with acute drug allergy to carbamazepine, phenytoin, allopurinol, or paracetamol confirms the in vitro data, because all patients had activated CD4+ or CD8+ T cells in the circulation. Our data clearly show the involvement of drug-specific T cells in drug allergies.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.155.1.462
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 1995
    detail.hit.zdb_id: 1475085-5
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  • 3
    Online Resource
    Online Resource
    Increased Sequence Diversity Coverage Improves Detection of HIV-Specific T Cell Responses
    The American Association of Immunologists ; 2007
    In:  The Journal of Immunology Vol. 179, No. 10 ( 2007-11-15), p. 6638-6650
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 179, No. 10 ( 2007-11-15), p. 6638-6650
    Abstract: The accurate identification of HIV-specific T cell responses is important for determining the relationship between immune response, viral control, and disease progression. HIV-specific immune responses are usually measured using peptide sets based on consensus sequences, which frequently miss responses to regions where test set and infecting virus differ. In this study, we report the design of a peptide test set with significantly increased coverage of HIV sequence diversity by including alternative amino acids at variable positions during the peptide synthesis step. In an IFN-γ ELISpot assay, these “toggled” peptides detected HIV-specific CD4+ and CD8+ T cell responses of significantly higher breadth and magnitude than matched consensus peptides. The observed increases were explained by a closer match of the toggled peptides to the autologous viral sequence. Toggled peptides therefore afford a cost-effective and significantly more complete view of the host immune response to HIV and are directly applicable to other variable pathogens.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.179.10.6638
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2007
    detail.hit.zdb_id: 1475085-5
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  • 4
    Online Resource
    Online Resource
    Cross-reactivity of T cell lines and clones to beta-lactam antibiotics.
    The American Association of Immunologists ; 1996
    In:  The Journal of Immunology Vol. 157, No. 3 ( 1996-08-01), p. 1071-1079
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 157, No. 3 ( 1996-08-01), p. 1071-1079
    Abstract: To clarify on a molecular level the specific T cell response to haptens like penicillin G, we generated T cell lines and clones from penicillin-allergic patients. Two types of beta-lactam reactivity of T cells could be delineated: one group of patients showed a rather restricted specificity, as the penicillin-elicited T cell lines generated from such donors proliferated only to the stimulating penicillin, but not to other beta-lactam antibiotics nor to cephalosporines, even if the side chain was identical. This indicates that the penicilloyl structure together with the side chain was recognized by these T cells. The second group comprised patients with more broadly reactive T cells, as they were restimulated by penicillin G as well as by related penicillins like amoxicillin or ampicillin, but not cephalosporines. This indicates that the penicilloyl structure, a common motif of penicillins, was important for T cell recognition. Clones generated from a broadly reactive patient confirmed this heterogeneity, as either monospecific or broadly specific T cell clones could be identified. This broad or very restricted pattern of T cell reactivity was reflected in the use of TCR Vbeta-chains: while the broadly reactive T cell lines showed a heterogenous TCR usage, the highly restricted T cell lines showed an up-regulation of one TCR Vbeta-chain. Thus, our data suggest that the outgrowth of T cells bearing a certain TCR Vbeta may be a sign of a limited cross-reactivity.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.157.3.1071
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 1996
    detail.hit.zdb_id: 1475085-5
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  • 5
    Online Resource
    Online Resource
    Heterogeneous T cell responses to beta-lactam-modified self-structures are observed in penicillin-allergic individuals.
    The American Association of Immunologists ; 1995
    In:  The Journal of Immunology Vol. 155, No. 5 ( 1995-09-01), p. 2670-2678
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 155, No. 5 ( 1995-09-01), p. 2670-2678
    Abstract: To investigate the role of T cells in drug allergy, we stimulated PBMC from penicillin-allergic patients with reactive penicillin G itself or penicillin G coupled with human serum albumin (BPO-HSA). T cell clones specific for penicillin G or BPO-HSA were established and their phenotype and reactivity to both forms of the beta-lactam were analyzed. T cell clones stimulated by penicillin G were CD4 and CD8 positive, whereas BPO-HSA stimulated the growth of CD4+ T cells. The penicillin G-specific clones were HLA class I or class II restricted and processing was not required as fixed APC could still present penicillin G. In contrast, BPO-HSA has to undergo processing to stimulate BPO-HSA-specific T cell clones. In addition to classical APC, activated MHC class II expressing T cells could also restimulate the penicillin G-specific clones, indicating that various cell types might serve as APC. Penicillin G and BPO-HSA-specific T cell clones produced a heterogeneous cytokine pattern as most clones produced high amounts of IL-2, IFN-gamma, TFN-alpha, and rather variable levels of IL-4 and IL-5. Since no Ag processing was required, penicillin G may stimulate T cells by binding directly to MHC molecules on the cell surface or to their embedded peptide. Alternatively, it may bind to soluble proteins like HSA, which are processed and subsequently presented in an immunogenic form. These different modes of presentation, which elicit a variety of immunological reactivities, may explain the great heterogeneity of the clinical pictures seen in penicillin allergy.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.155.5.2670
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 1995
    detail.hit.zdb_id: 1475085-5
    Location Call Number Limitation Availability
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