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  • 1
    Publication Date: 1998-06-20
    Description: In humans, interferon gamma (IFN-gamma) receptor deficiency leads to a predisposition to mycobacterial infections and impairs the formation of mature granulomas. Interleukin-12 (IL-12) receptor deficiency was found in otherwise healthy individuals with mycobacterial infections. Mature granulomas were seen, surrounded by T cells and centered with epithelioid and multinucleated giant cells, yet reduced IFN-gamma concentrations were found to be secreted by activated natural killer and T cells. Thus, IL-12-dependent IFN-gamma secretion in humans seems essential in the control of mycobacterial infections, despite the formation of mature granulomas due to IL-12-independent IFN-gamma secretion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Altare, F -- Durandy, A -- Lammas, D -- Emile, J F -- Lamhamedi, S -- Le Deist, F -- Drysdale, P -- Jouanguy, E -- Doffinger, R -- Bernaudin, F -- Jeppsson, O -- Gollob, J A -- Meinl, E -- Segal, A W -- Fischer, A -- Kumararatne, D -- Casanova, J L -- New York, N.Y. -- Science. 1998 May 29;280(5368):1432-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM U429, Hopital Necker-Enfants Malades, Paris 75015, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9603732" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cytotoxicity, Immunologic ; Female ; Granuloma/immunology ; Humans ; Hypersensitivity, Delayed ; Interferon-gamma/biosynthesis/immunology/secretion ; Interleukin-12/*immunology ; Killer Cells, Natural/immunology ; Lymphocyte Activation ; Male ; Mice ; Mice, Knockout ; Mutation ; Mycobacterium avium-intracellulare Infection/*immunology ; *Mycobacterium bovis ; Pedigree ; Receptors, Interferon/genetics/immunology ; Receptors, Interleukin/deficiency/*genetics ; Receptors, Interleukin-12 ; T-Lymphocytes/immunology ; Tuberculosis/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 1998-06-20
    Description: Interleukin-12 (IL-12) is a cytokine that promotes cell-mediated immunity to intracellular pathogens by inducing type 1 helper T cell (TH1) responses and interferon-gamma (IFN-gamma) production. IL-12 binds to high-affinity beta1/beta2 heterodimeric IL-12 receptor (IL-12R) complexes on T cell and natural killer cells. Three unrelated individuals with severe, idiopathic mycobacterial and Salmonella infections were found to lack IL-12Rbeta1 chain expression. Their cells were deficient in IL-12R signaling and IFN-gamma production, and their remaining T cell responses were independent of endogenous IL-12. IL-12Rbeta1 sequence analysis revealed genetic mutations that resulted in premature stop codons in the extracellular domain. The lack of IL-12Rbeta1 expression results in a human immunodeficiency and shows the essential role of IL-12 in resistance to infections due to intracellular bacteria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Jong, R -- Altare, F -- Haagen, I A -- Elferink, D G -- Boer, T -- van Breda Vriesman, P J -- Kabel, P J -- Draaisma, J M -- van Dissel, J T -- Kroon, F P -- Casanova, J L -- Ottenhoff, T H -- New York, N.Y. -- Science. 1998 May 29;280(5368):1435-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunohematology and Bloodbank, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, the Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9603733" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Child, Preschool ; Codon, Terminator ; Disease Susceptibility ; Female ; Frameshift Mutation ; Genes, Recessive ; Humans ; Interferon-gamma/biosynthesis ; Interleukin-12/*immunology/metabolism ; Lymphocyte Activation ; Mutation ; Mycobacterium avium-intracellulare Infection/*immunology ; *Mycobacterium bovis ; Receptors, Interferon/metabolism ; Receptors, Interleukin/deficiency/*genetics/metabolism ; Receptors, Interleukin-12 ; Salmonella Infections/*immunology ; Sequence Deletion ; T-Lymphocytes/immunology ; Tuberculosis/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 1995-04-28
    Description: Parasite-specific CD4+ T cells have been shown to transfer protection against Leishmania major in susceptible BALB/c mice. An epitope-tagged expression library was used to identify the antigen recognized by a protective CD4+ T cell clone. The expression library allowed recombinant proteins made in bacteria to be captured by macrophages for presentation to T cells restricted to major histocompatibility complex class II. A conserved 36-kilodalton member of the tryptophan-aspartic acid repeat family of proteins was identified that was expressed in both stages of the parasite life cycle. A 24-kilodalton portion of this antigen protected susceptible mice when administered as a vaccine with interleukin-12 before infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mougneau, E -- Altare, F -- Wakil, A E -- Zheng, S -- Coppola, T -- Wang, Z E -- Waldmann, R -- Locksley, R M -- Glaichenhaus, N -- AI26918/AI/NIAID NIH HHS/ -- T32 DK07007/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1995 Apr 28;268(5210):563-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Pharmacologie Moleculaire et Cellulaire, UPR411 CNRS, Valbonne, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7725103" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigens, Protozoan/chemistry/genetics/*immunology ; Cloning, Molecular ; Histocompatibility Antigens Class II/immunology ; Immunodominant Epitopes ; Interleukin-12/administration & dosage ; Interleukin-4/immunology ; Leishmania major/genetics/*immunology ; Leishmaniasis, Cutaneous/*prevention & control ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Protozoan Proteins/chemistry/genetics/*immunology ; Protozoan Vaccines/immunology ; Th1 Cells/*immunology ; Vaccines, Synthetic/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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