Synovial fluids of patients with rheumatoid arthritis, osteoarthritis, psoriatic arthritis, react... more Synovial fluids of patients with rheumatoid arthritis, osteoarthritis, psoriatic arthritis, reactive arthritis and Reiter's syndrome were examined for their concentrations of interleukin 6 (IL-6) in a proliferation assay with the IL-6 dependent hybridoma cell line B13.29 (subclone B9). IL-6 activity was significantly higher in the synovial fluids of patients with rheumatoid arthritis and psoriatic arthritis than in patients with osteoarthritis. Significant correlations were shown between the concentrations of synovial fluid IL-6 and IgG. These findings may contribute to the understanding of the enhanced immunoglobulin production by synovial mononuclear cells in patients with inflammatory joint disease.
A: Development of T Lymphocytes in the Thymus.- Introductory Remarks.- Development of T Lymphocyt... more A: Development of T Lymphocytes in the Thymus.- Introductory Remarks.- Development of T Lymphocytes Within the Thymus and Within Thymic Nurse Cells. With 3 Figures.- Thymus Development.- Major Histocompatibility-Restricted Cytolytic T-Lymphocyte Precursors from the Thymus of In Vivo Primed Mice: Increased Frequency and Resistance to Anti-Lyt-2 Antibody Inhibition. With 1 Figure.- Thymic Stem Cells: Their Interaction with the Thymic Stroma and Tolerance Induction.- B: Murine T-Cell Receptor Genes.- Organization, Rearrangement, and Diversification of Mouse T-Cell Receptor Genes. With 1 Figure.- Expression of T-Cell Receptor by a Mouse Monoclonal Antigen-Specific Suppressor T-Cell Line.- Somatic Variation of Antigen-Recognition Specificity in H-2b-TNP-Specific Cytotoxic T-Cell Clones.- The Change of Specificity, Karyotype, and Antigen-Receptor Gene Expression is Correlated in Cytotoxic T-Cell Lines.- C: Phenotype and Functional Potential of T-Cell Clones.- Introductory Remarks.- A Study of the Functional Potential of Mouse T-Cell Clones.- Generation, Propagation, and Variation in Cloned, Antigen-Specific, Ia-Restricted Cytolytic T-Cell Lines.- Significance of T4 or T8 Phenotype of Human Cytotoxic T-Lymphocyte Clones. With 1 Figure.- Natural and Unnatural Killing by Cytolytic T Lymphocytes. With 2 Figures.- Acquisition of Suppressive and Natural Killer-Like Activities Associated with Loss of Alloreactivity in Human "Helper" T-Lymphocyte Clones. With 3 Figures.- Expression and Function of Class II I-Ak Antigens on an Antigen-Specific T-Suppressor Cell Clone. With 2 Figures.- D: Signal Requirements for T-Cell Activation.- Introductory Remarks.- Heterogeneity of the Signal Requirements During the Primary Activation of Resting Lyt-2+ Cytotoxic T-Lymphocyte (CTL) Precursors into Clonally Developing CTL. With 2 Figures.- Regulation of Lytic Function by Recombinant IL2 and Antigen. With 4 Figures.- The Target Structure for T11: A Cell Interaction Molecule Involved in T-Cell Activation? With 3 Figures.- Antigen- and Lectin- Sensitized Murine Cytolytic T Lymphocyte- Precursors Require Both Interleukin 2 and Endogenously Produced Immune (?) Interferon for Their Growth and Differentiation. With 3 Figures.- Activation Requirements for Resting T Lymphocytes.- E: Self-Nonself Discrimination in the T-Cell Compartment.- Introductory Remarks.- Functional Clonal Deletion and Suppression as Complementary Mechanisms in T Lymphocyte Tolerance.- Human T Cell Clones, Tolerance, and the Analysis of Autoimmunity. With 1 Figure.- Antiself Suppressive (Veto) Activity of Responder Cells in Mixed Lymphocyte Cultures. With 6 Figures.- Analysis of T Suppressor Cell Mediated Tumor Escape Mechanisms. With 2 Figures.- The T-Cell Receptor Recognizes Nominal and Self Antigen Independently. A Theoretical Alternative to the Modified Self Concept. With 3 Figures.- F: T-Cell-Mediated Autoreactivity.- Introductory Remarks.- T-Cell Reactivity to Polymorphic MHC Determinants. I. MHC-Guided T-Cell Reactivity.- T-Cell Reactivity to Polymorphic MHC Determinants. II. Self-Reactive and Self-Restricted T Cells. With 6 Figures.- T-Cell Reactivity to Polymorphic MHC Determinants. III. Alloreactive and Allorestricted T Cells. With 9 Figures.- Appearance of New Specificities in Lectin-Induced T-Cell Clones Obtained from Limiting Dilution T-Cell Cultures. With 2 Figures.- Syngeneic Cytotoxicity and Veto Activity in Thymic Lymphoid Colonies and Their Expanded Progeny. With 4 Figures.- Functional Analysis of a Self-I-A Reactive T-Cell Clone Which Preferentially Stimulates Activated B Cells.- Indexed in Current Contents.
... 1). (Published with permission from Biochem. J. 239, p. 764 ~ 1986 The Biochemical Society, L... more ... 1). (Published with permission from Biochem. J. 239, p. 764 ~ 1986 The Biochemical Society, London.) References Edith Sire 1 sire, E. and Cross, 53 (1986) 8iochem. ... (1987)Nature 328, 626-629 23 Fazekas de St Groth, B., Gallagher, PF and Miller, JFAP (1986) Proc. ...
This study addresses the role of a bacterial superantigen as a potential virulence factor during ... more This study addresses the role of a bacterial superantigen as a potential virulence factor during an acute systemic infection. BALB/c mice were intravenously infected with a recombinant Staphylococcus aureus strain capable of producing plasmid-encoded staphylococcal enterotoxin B (SEB) or with the SEB plasmid-deficient parental strain. Infection with SEB-producing bacteria resulted in an initial expansion and subsequent decrease of circulating V beta 8+ T lymphocytes. This numeric decrease was accompanied by a SEB-specific state of hyporesponsiveness of splenic T cells. In parallel with SEB-triggered unresponsiveness of a large proportion of T lymphocytes, a weakening of the overall T cell responsiveness towards the invading bacteria was found. Furthermore, the production of SEB altered the kinetics of bacterial clearance: Animals infected with the SEB-producing variant showed a significantly elevated bacterial burden and could less efficiently clear the bacteria. However, the overall effect of SEB production on the course of bacterial infection was surprisingly weak, suggesting that the superantigen was only a minor virulence factor for the bacterium.
The idiopathic hypereosinophilic syndrome (HES) comprises a heterogeneous group of disorders with... more The idiopathic hypereosinophilic syndrome (HES) comprises a heterogeneous group of disorders with unknown pathogenesis characterized by persistent peripheral blood and bone marrow eosinophilia and eosinophilic infiltrates of multiple organs leading to severe organ dysfunction. In the present study, T lymphocyte clones were randomly established from the blood of a patient with HES and propagated in culture with mitogen and interleukin 2. Whereas 28 of 29 clones were able to stimulate myeloid colony formation when co-cultured with normal bone marrow cells in a double-layer micro-agar culture system, one third of these clones preferentially stimulated pure eosinophil colonies (up to 98% of all colonies). This pattern differed markedly (p less than 0.001) from the pattern of release of hemopoietic factors by 126 T cell clones established from four other individuals. Eosinophil colony stimulation was due to the release of a lineage-specific eosinophilic colony-stimulating factor (Eo-CSF) by these clones after appropriate stimulation. Production of Eo-CSF in vitro was inhibited by hydrocortisone or cyclosporin A. All Eo-CSF-producing clones had the T4+8-phenotype and were capable of producing in addition interleukin 2 and interferon-gamma. Southern blot analysis of the T cell receptor beta-chain rearrangement of the Eo-CSF-producing clones showed a different rearrangement pattern for each clone. These studies suggest a reactive T cell-mediated eosinophilia as the pathogenetic mechanism in this case of HES and, for the first time, point to a biologic relevance of a lymphokine-induced stimulation of hemopoiesis.
Synovial fluids of patients with rheumatoid arthritis, osteoarthritis, psoriatic arthritis, react... more Synovial fluids of patients with rheumatoid arthritis, osteoarthritis, psoriatic arthritis, reactive arthritis and Reiter's syndrome were examined for their concentrations of interleukin 6 (IL-6) in a proliferation assay with the IL-6 dependent hybridoma cell line B13.29 (subclone B9). IL-6 activity was significantly higher in the synovial fluids of patients with rheumatoid arthritis and psoriatic arthritis than in patients with osteoarthritis. Significant correlations were shown between the concentrations of synovial fluid IL-6 and IgG. These findings may contribute to the understanding of the enhanced immunoglobulin production by synovial mononuclear cells in patients with inflammatory joint disease.
A: Development of T Lymphocytes in the Thymus.- Introductory Remarks.- Development of T Lymphocyt... more A: Development of T Lymphocytes in the Thymus.- Introductory Remarks.- Development of T Lymphocytes Within the Thymus and Within Thymic Nurse Cells. With 3 Figures.- Thymus Development.- Major Histocompatibility-Restricted Cytolytic T-Lymphocyte Precursors from the Thymus of In Vivo Primed Mice: Increased Frequency and Resistance to Anti-Lyt-2 Antibody Inhibition. With 1 Figure.- Thymic Stem Cells: Their Interaction with the Thymic Stroma and Tolerance Induction.- B: Murine T-Cell Receptor Genes.- Organization, Rearrangement, and Diversification of Mouse T-Cell Receptor Genes. With 1 Figure.- Expression of T-Cell Receptor by a Mouse Monoclonal Antigen-Specific Suppressor T-Cell Line.- Somatic Variation of Antigen-Recognition Specificity in H-2b-TNP-Specific Cytotoxic T-Cell Clones.- The Change of Specificity, Karyotype, and Antigen-Receptor Gene Expression is Correlated in Cytotoxic T-Cell Lines.- C: Phenotype and Functional Potential of T-Cell Clones.- Introductory Remarks.- A Study of the Functional Potential of Mouse T-Cell Clones.- Generation, Propagation, and Variation in Cloned, Antigen-Specific, Ia-Restricted Cytolytic T-Cell Lines.- Significance of T4 or T8 Phenotype of Human Cytotoxic T-Lymphocyte Clones. With 1 Figure.- Natural and Unnatural Killing by Cytolytic T Lymphocytes. With 2 Figures.- Acquisition of Suppressive and Natural Killer-Like Activities Associated with Loss of Alloreactivity in Human "Helper" T-Lymphocyte Clones. With 3 Figures.- Expression and Function of Class II I-Ak Antigens on an Antigen-Specific T-Suppressor Cell Clone. With 2 Figures.- D: Signal Requirements for T-Cell Activation.- Introductory Remarks.- Heterogeneity of the Signal Requirements During the Primary Activation of Resting Lyt-2+ Cytotoxic T-Lymphocyte (CTL) Precursors into Clonally Developing CTL. With 2 Figures.- Regulation of Lytic Function by Recombinant IL2 and Antigen. With 4 Figures.- The Target Structure for T11: A Cell Interaction Molecule Involved in T-Cell Activation? With 3 Figures.- Antigen- and Lectin- Sensitized Murine Cytolytic T Lymphocyte- Precursors Require Both Interleukin 2 and Endogenously Produced Immune (?) Interferon for Their Growth and Differentiation. With 3 Figures.- Activation Requirements for Resting T Lymphocytes.- E: Self-Nonself Discrimination in the T-Cell Compartment.- Introductory Remarks.- Functional Clonal Deletion and Suppression as Complementary Mechanisms in T Lymphocyte Tolerance.- Human T Cell Clones, Tolerance, and the Analysis of Autoimmunity. With 1 Figure.- Antiself Suppressive (Veto) Activity of Responder Cells in Mixed Lymphocyte Cultures. With 6 Figures.- Analysis of T Suppressor Cell Mediated Tumor Escape Mechanisms. With 2 Figures.- The T-Cell Receptor Recognizes Nominal and Self Antigen Independently. A Theoretical Alternative to the Modified Self Concept. With 3 Figures.- F: T-Cell-Mediated Autoreactivity.- Introductory Remarks.- T-Cell Reactivity to Polymorphic MHC Determinants. I. MHC-Guided T-Cell Reactivity.- T-Cell Reactivity to Polymorphic MHC Determinants. II. Self-Reactive and Self-Restricted T Cells. With 6 Figures.- T-Cell Reactivity to Polymorphic MHC Determinants. III. Alloreactive and Allorestricted T Cells. With 9 Figures.- Appearance of New Specificities in Lectin-Induced T-Cell Clones Obtained from Limiting Dilution T-Cell Cultures. With 2 Figures.- Syngeneic Cytotoxicity and Veto Activity in Thymic Lymphoid Colonies and Their Expanded Progeny. With 4 Figures.- Functional Analysis of a Self-I-A Reactive T-Cell Clone Which Preferentially Stimulates Activated B Cells.- Indexed in Current Contents.
... 1). (Published with permission from Biochem. J. 239, p. 764 ~ 1986 The Biochemical Society, L... more ... 1). (Published with permission from Biochem. J. 239, p. 764 ~ 1986 The Biochemical Society, London.) References Edith Sire 1 sire, E. and Cross, 53 (1986) 8iochem. ... (1987)Nature 328, 626-629 23 Fazekas de St Groth, B., Gallagher, PF and Miller, JFAP (1986) Proc. ...
This study addresses the role of a bacterial superantigen as a potential virulence factor during ... more This study addresses the role of a bacterial superantigen as a potential virulence factor during an acute systemic infection. BALB/c mice were intravenously infected with a recombinant Staphylococcus aureus strain capable of producing plasmid-encoded staphylococcal enterotoxin B (SEB) or with the SEB plasmid-deficient parental strain. Infection with SEB-producing bacteria resulted in an initial expansion and subsequent decrease of circulating V beta 8+ T lymphocytes. This numeric decrease was accompanied by a SEB-specific state of hyporesponsiveness of splenic T cells. In parallel with SEB-triggered unresponsiveness of a large proportion of T lymphocytes, a weakening of the overall T cell responsiveness towards the invading bacteria was found. Furthermore, the production of SEB altered the kinetics of bacterial clearance: Animals infected with the SEB-producing variant showed a significantly elevated bacterial burden and could less efficiently clear the bacteria. However, the overall effect of SEB production on the course of bacterial infection was surprisingly weak, suggesting that the superantigen was only a minor virulence factor for the bacterium.
The idiopathic hypereosinophilic syndrome (HES) comprises a heterogeneous group of disorders with... more The idiopathic hypereosinophilic syndrome (HES) comprises a heterogeneous group of disorders with unknown pathogenesis characterized by persistent peripheral blood and bone marrow eosinophilia and eosinophilic infiltrates of multiple organs leading to severe organ dysfunction. In the present study, T lymphocyte clones were randomly established from the blood of a patient with HES and propagated in culture with mitogen and interleukin 2. Whereas 28 of 29 clones were able to stimulate myeloid colony formation when co-cultured with normal bone marrow cells in a double-layer micro-agar culture system, one third of these clones preferentially stimulated pure eosinophil colonies (up to 98% of all colonies). This pattern differed markedly (p less than 0.001) from the pattern of release of hemopoietic factors by 126 T cell clones established from four other individuals. Eosinophil colony stimulation was due to the release of a lineage-specific eosinophilic colony-stimulating factor (Eo-CSF) by these clones after appropriate stimulation. Production of Eo-CSF in vitro was inhibited by hydrocortisone or cyclosporin A. All Eo-CSF-producing clones had the T4+8-phenotype and were capable of producing in addition interleukin 2 and interferon-gamma. Southern blot analysis of the T cell receptor beta-chain rearrangement of the Eo-CSF-producing clones showed a different rearrangement pattern for each clone. These studies suggest a reactive T cell-mediated eosinophilia as the pathogenetic mechanism in this case of HES and, for the first time, point to a biologic relevance of a lymphokine-induced stimulation of hemopoiesis.
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