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David H Presky - One of the best experts on this subject based on the ideXlab platform.

  • Dysregulation of Lymphocyte Interleukin-12 Receptor Expression in Sézary Syndrome
    Journal of Investigative Dermatology, 2001
    Co-Authors: Mohamed H. Zaki, David H Presky, Ryan B. Shane, Yuemei Geng, Suzanne E. Everetts, Maria Wysocka, Louise C. Showe, Jonni S. Moore, Alain H Rook
    Abstract:

    Initial phase I and II clinical trials with recombinant human Interleukin-12 have demonstrated the therapeutic efficacy of this cytokine in early stage cutaneous T cell lymphoma as compared with more advanced stages such as the leukemic Sezary syndrome. In an effort to optimize the use of recombinant human Interleukin-12, using flow cytometry we studied the regulation of the Interleukin-12 receptor β1 (high affinity chain) and β2 (chain necessary for Interleukin-12 signal transduction) on normal volunteer CD4 + and CD8 + T cells and CD4 + and CD8 + cells from eight patients with different degrees of leukemic involvement with Sezary syndrome. The β1 chain was not readily detectable on resting normal and T cells from Sezary patients, but expression was induced following T cell activation with phytohemagglutinin. Similarly, the β2 chain was not detectable on resting normal volunteer T cells, but could be induced following phytohemagglutinin stimulation. Moreover, the β2 chain on normal volunteer T cells was markedly upregulated following short-term culture with interferon-γ or recombinant human Interleukin-12. CD8 + T cells routinely exhibited a greater expression of β2 than did CD4 + T cells. In marked contrast, both CD4 + and CD8 + T cells from patients with Sezary syndrome and a high tumor cell burden (> 50% circulating atypical Sezary T cells) failed to express the β2 chain under any culture conditions. Although, culture with anti-Interleukin-10 also markedly increased β2 expression on normal volunteer T cells, this failed to induce expression on either CD4 + or CD8 + T cells from Sezary patients and a high tumor burden. Investigation of patients with Sezary syndrome and a low tumor cell burden ( + and CD8 + peripheral blood T cells from these earlier stage patients were induced to express the β2 chain, although at a lower frequency of positivity than T cells from normals, following culture with phytohemagglutinin, interferon-γ, recombinant human Interleukin-12, or anti-Interleukin-10. These results indicate that short-term culture with interferon-γ and recombinant human Interleukin-12 potently upregulates β2 chain expression on T cells from normal volunteers, whereas a similar, but less marked effect occurs on T cells from Sezary syndrome patients and a low circulating tumor cell burden. In contrast, the β2 chain appears to be suppressed on both CD4 + and CD8 + T cells from Sezary patients with a heavy circulating tumor cell burden and it is not induced by interferon-γ or recombinant human Interleukin-12. Therefore, recombinant human Interleukin-12 is likely to be most effective for early stage cutaneous T cell lymphoma due to a greater display of β2 receptors on responding CD8 + anti-tumor cytotoxic T cells.

  • the Interleukin 12 Interleukin 12 receptor system role in normal and pathologic immune responses
    Annual Review of Immunology, 1998
    Co-Authors: Maurice K Gately, Jeanne Magram, Alvin S Stern, Luciano Adorini, Louis M Renzetti, Ueli Gubler, David H Presky
    Abstract:

    ▪ Abstract Interleukin-12 (IL-12) is a heterodimeric cytokine that plays a central role in promoting type 1 T helper cell (Th1) responses and, hence, cell-mediated immunity. Its activities are mediated through a high-affinity receptor composed of two subunits, designated β1 and β2. Of these two subunits, β2 is more restricted in its distribution, and regulation of its expression is likely a central mechanism by which IL-12 responsiveness is controlled. Studies with neutralizing anti-IL-12 antibodies and IL-12-deficient mice have suggested that endogenous IL-12 plays an important role in the normal host defense against infection by a variety of intracellular pathogens. However, IL-12 appears also to play a central role in the genesis of some forms of immunopathology. Inhibition of IL-12 synthesis or activity may be beneficial in diseases associated with pathologic Th1 responses, such as multiple sclerosis or Crohn's disease. On the other hand, administration of recombinant IL-12 may have utility in the tre...

  • THE Interleukin-12/Interleukin-12-RECEPTOR SYSTEM: Role in Normal and Pathologic Immune Responses
    Annual Review of Immunology, 1998
    Co-Authors: Maurice K Gately, Jeanne Magram, Alvin S Stern, Luciano Adorini, Louis M Renzetti, Ueli Gubler, David H Presky
    Abstract:

    ▪ Abstract Interleukin-12 (IL-12) is a heterodimeric cytokine that plays a central role in promoting type 1 T helper cell (Th1) responses and, hence, cell-mediated immunity. Its activities are mediated through a high-affinity receptor composed of two subunits, designated β1 and β2. Of these two subunits, β2 is more restricted in its distribution, and regulation of its expression is likely a central mechanism by which IL-12 responsiveness is controlled. Studies with neutralizing anti-IL-12 antibodies and IL-12-deficient mice have suggested that endogenous IL-12 plays an important role in the normal host defense against infection by a variety of intracellular pathogens. However, IL-12 appears also to play a central role in the genesis of some forms of immunopathology. Inhibition of IL-12 synthesis or activity may be beneficial in diseases associated with pathologic Th1 responses, such as multiple sclerosis or Crohn's disease. On the other hand, administration of recombinant IL-12 may have utility in the tre...

Lutfiye Mesci - One of the best experts on this subject based on the ideXlab platform.

Ge Zheng-long - One of the best experts on this subject based on the ideXlab platform.

  • The expression of human Interleukin 12 in transgenic potato by confocal laser scanning microscopy
    2008
    Co-Authors: Ge Zheng-long
    Abstract:

    Objective To investigate the expression of exogenous human Interleukin-12 gene in the transgenic potato. Methods The transgenic potatoes were collected, and wild potato acted as negative control. The expression of hIL-12 in the stem and tuber were detected by indirect immunofluorescent marking and confocal laser scanning microscopy. Results Human Interleukin 12 expression was observed in the stem and tuber of transgenic potatoes by confocal laser scanning microscope. Conclusions The hIL-12 is detected in the stem and tuber of transgenic potato expression system established by our research group.

  • The expression of human Interleukin 12 in transgenic potato expression system
    2007
    Co-Authors: Ge Zheng-long
    Abstract:

    Objective To investigate the expression of human Interleukin 12 in transgenic potatoes established by our research group.Methods The expression of human Interleukin 12 in transgenic potatoes were tested by ELISA.Results Human Interleukin 12 production in the leaves and tubers of 2 transgenic potatoes was obviously different from that of control group(P 0.01).The plant-produced hIL-12 in the 5～7 filial generation were not obviously different from each other.Conclusions The human Interleukin 12 was expressed in our established transgenic potato expression system and the genetic characters are stable.

Amy S Paller - One of the best experts on this subject based on the ideXlab platform.

  • In Vivo Gene Therapy with Interleukin-12 Inhibits Primary Vascular Tumor Growth and Induces Apoptosis in a Mouse Model
    Journal of Investigative Dermatology, 1999
    Co-Authors: Chong Wang, M. Eugenia Quevedo, Brian Lannutti, Kenneth B. Gordon, Amy S Paller
    Abstract:

    Interleukin-12 is proposed to have anti-neoplastic activity on the basis of both its anti-angiogenic and immunologic effects. Gene gun therapy with Interleukin-12 cDNA into the peritumoral area of immunocompetent 129/J mice with life-threatening primary vascular tumors reduced tumor volume 7.5-fold and almost tripled the duration of mouse survival, in contrast with luciferase-bombarded control mice. Epidermal expression of mouse Interleukin-12 elevated tumoral and serum levels of interferon-γ and tumor necrosis factor-α, increased the tumoral populations of T lymphocyte and natural killer cells, and induced tumor apoptosis. Gene transfer of Interleukin-12 had little effect on tumor volumes and survival of tumor-bearing athymic nude mice, emphasizing the requirement for T cell directed cellular immunity. Peritumoral gene gun introduction of Interleukin-12 may be a novel, cost-effective approach to limit the growth and associated mortality of life-threatening tumors.

  • In Vivo Gene Therapy with Interleukin-12 Inhibits Primary Vascular Tumor Growth and Induces Apoptosis in a Mouse Model
    Journal of Investigative Dermatology, 1999
    Co-Authors: Chong Wang, M. Eugenia Quevedo, Brian Lannutti, Kenneth B. Gordon, Amy S Paller
    Abstract:

    Interleukin-12 is proposed to have anti-neoplastic activity on the basis of both its anti-angiogenic and immunologic effects. Gene gun therapy with Interleukin-12 cDNA into the peritumoral area of immunocompetent 129/J mice with life-threatening primary vascular tumors reduced tumor volume 7.5-fold and almost tripled the duration of mouse survival, in contrast with luciferase-bombarded control mice. Epidermal expression of mouse Interleukin-12 elevated tumoral and serum levels of interferon-γ and tumor necrosis factor-α, increased the tumoral populations of T lymphocyte and natural killer cells, and induced tumor apoptosis. Gene transfer of Interleukin-12 had little effect on tumor volumes and survival of tumor-bearing athymic nude mice, emphasizing the requirement for T cell directed cellular immunity. Peritumoral gene gun introduction of Interleukin-12 may be a novel, cost-effective approach to limit the growth and associated mortality of life-threatening tumors.

Giorgio Trinchieri - One of the best experts on this subject based on the ideXlab platform.

  • Immunobiology of Interleukin-12.
    Immunologic research, 1998
    Co-Authors: Giorgio Trinchieri
    Abstract:

    Interleukin-12 (IL12) is a heterodimeric cytokine which is produced by phagocytic cells and antigen-presenting cells within a few hours of infection, particularly in the case of bacteria and intracellular parasites, and acts as a proinflammatory cytokine, activating natural killer (NK) cells, and, through its ability to induce interferon-gamma(IFN gamma) production, enhancing the phagocytic and bacteriocidal activity of phagocytic cells and their ability to release proinflammatory cytokines, including IL12 itself. Furthermore, IL12 produced during the early phases of infection and inflammation, sets the stage for the ensuing antigen-specific immune response, favoring differentiation and function of T helper type 1 (Th1) T cells while inhibiting the differentiation of Th2 T cells. Thus, IL12, in addition to being a potent proinflammatory cytokine, is a key immunoregulator molecule in Th1 responses.

  • Biological properties and therapeutic applications of Interleukin-12
    European Cytokine Network, 1997
    Co-Authors: Giorgio Trinchieri
    Abstract:

    Interleukin-12 (IL-12) is a heterodimeric cytokine produced by phagocytic cells and antigen-presenting cells within a few hours of infection, particularly in the case of bacteria and intracellular parasites, and acts as a proinflammatory cytokine, activating natural killer (NK) cells, and, through its ability to induce interferon-gamma (IFN-gamma) production, enhancing the phagocytic and bactericidal activity of phagocytic cells and [...]

  • Function and clinical use of Interleukin-12.
    Current Opinion in Hematology, 1997
    Co-Authors: Giorgio Trinchieri
    Abstract:

    Interleukin-12 is a heterodimeric cytokine produced by phagocytic cells, professional antigen-presenting cells such as dendritic cells and skin Langerhans cells, and B cells. Interleukin-12 production is induced by bacteria, intracellular pathogens, fungi, viruses, or their products in a T-cell-independent pathway or a T-cell-dependent pathway, the latter mediated through CD40 ligand-CD40 interaction. Interleukin-12 is produced rapidly after infection and acts as a proinflammatory cytokine eliciting production of interferon gamma, by T and natural killer cells, which activates phagocytic cells. The production of Interleukin-12 is strictly regulated by positive and negative feedback mechanisms. If Interleukin-12 and Interleukin-12-induced interferon gamma are present during early T-cell expansion in response to antigen, T-helper type-1 cell generation is favored and generation of T-helper type-2 cells is inhibited. Thus Interleukin-12 is also a potent immunoregulatory cytokine that promotes T-helper type-1 differentiation and is instrumental in the T-helper type-1-dependent resistance to infections by bacteria, intracellular parasites, fungi, and certain viruses. By inhibiting T-helper type-2 cell response, Interleukin-12 has a suppressive effect on allergic reactions; by promoting T-helper type-1 responses it participates in the immunopathology responsible for several organ-specific autoimmune diseases. Viruses inducing a permanent or transient immunodepression, such as HIV and measles, may act, in part, by suppressing Interleukin-12 production. Because of its ability to enhance resistance to several infectious diseases and to act as an adjuvant in vaccination, and because of its powerful antitumor effect in vivo, Interleukin-12 is currently in clinical trials in cancer patients and HIV-infected patients, and it is being considered for therapeutic use in other diseases.

  • The role of Interleukin 12 in the immune response, disease and therapy
    Immunology Today, 1994
    Co-Authors: Giorgio Trinchieri, Phillip Scott
    Abstract:

    The heterodimeric cytokine Interleukin 12 (IL-12) stimulates cytotoxicity and cytokine production by T cells and natural killer (NK) cells, and initiates development of CD4+ T helper 1 (Th1) cells. A recent meeting defined how IL-12 contributes to immune responses in disease, as well as how IL-12 can be used to circumvent disease.

  • Interleukin-12 and its role in the generation of TH1 cells
    Immunology Today, 1993
    Co-Authors: Giorgio Trinchieri
    Abstract:

    Over the past few years a growing number of new cytokines have been discovered. Here, Giorgio Trinchieri reports on one of these, Interleukin 12, and discusses the significance of the many effects it has on the regulation of immunity and its importance to the generation of TH1 cells.