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Cornel Fraefel - One of the best experts on this subject based on the ideXlab platform.

Robbie B. Mailliard - One of the best experts on this subject based on the ideXlab platform.

  • Helper Function of memory cd8 t cells heterologous cd8 t cells support the induction of therapeutic cancer immunity
    Cancer Research, 2007
    Co-Authors: Yutaro Nakamura, Adam Giermasz, Payal Watchmaker, Julie Urban, Brian S. Sheridan, Fumihiko Nishimura, Kotaro Sasaki, Rachel Cumberland, Ravikumar Muthuswamy, Robbie B. Mailliard
    Abstract:

    In contrast to the well-established efficacy of preventive vaccines, the effectiveness of therapeutic vaccines remains limited. To develop effective vaccination regimens against cancer, we have analyzed the effect of effector and memory CD8+ T cells on the ability of dendritic cells to mediate the immunologic and antitumor effects of vaccination. We show that in contrast to effector CD8+ T cells that kill antigen-carrying dendritic cells, IFNγ-producing memory CD8+ T cells act as “Helper” cells, supporting the ability of dendritic cells to produce interleukin-12 (IL-12) p70. Promoting the interaction of tumor antigen-carrying dendritic cells with memory-type “heterologous” (tumor-irrelevant) CD8+ T cells strongly enhances the IL-12p70-dependent immunogenic and therapeutic effects of vaccination in the animals bearing established tumors. Our data show that the suppressive and Helper Functions of CD8+ T cells are differentially expressed at different phases of CD8+ T-cell responses. Selective performance of Helper Functions by memory (in contrast to effector) CD8+ T cells helps to explain the phenomenon of immune memory and facilitates the design of effective therapeutic vaccines against cancer and chronic infections. [Cancer Res 2007;67(20):10012–8

  • Helper Function of memory CD8+ T cells: Heterologous CD8 + T cells support the induction of therapeutic cancer immunity
    Cancer Research, 2007
    Co-Authors: Yutaro Nakamura, Adam Giermasz, Payal Watchmaker, Julie Urban, Brian S. Sheridan, Fumihiko Nishimura, Kotaro Sasaki, Rachel Cumberland, Ravikumar Muthuswamy, Robbie B. Mailliard
    Abstract:

    In contrast to the well-established efficacy of preventive vaccines, the effectiveness of therapeutic vaccines remains limited. To develop effective vaccination regimens against cancer, we have analyzed the effect of effector and memory CD8+ T cells on the ability of dendritic cells to mediate the immunologic and antitumor effects of vaccination. We show that in contrast to effector CD8+ T cells that kill antigen-carrying dendritic cells, IFNγ-producing memory CD8+ T cells act as “Helper” cells, supporting the ability of dendritic cells to produce interleukin-12 (IL-12) p70. Promoting the interaction of tumor antigen-carrying dendritic cells with memory-type “heterologous” (tumor-irrelevant) CD8+ T cells strongly enhances the IL-12p70-dependent immunogenic and therapeutic effects of vaccination in the animals bearing established tumors. Our data show that the suppressive and Helper Functions of CD8+ T cells are differentially expressed at different phases of CD8+ T-cell responses. Selective performance of Helper Functions by memory (in contrast to effector) CD8+ T cells helps to explain the phenomenon of immune memory and facilitates the design of effective therapeutic vaccines against cancer and chronic infections. [Cancer Res 2007;67(20):10012–8

  • Dendritic cells mediate NK cell help for Th1 and CTL responses: two-signal requirement for the induction of NK cell Helper Function.
    Journal of Immunology, 2003
    Co-Authors: Robbie B. Mailliard, Young Ik Son, Richard E. Redlinger, Patrick T. Coates, Adam Giermasz, Penelope A. Morel, Walter J. Storkus, Pawel Kalinski
    Abstract:

    Early stages of viral infections are associated with local recruitment and activation of dendritic cells (DC) and NK cells. Although activated DC and NK cells are known to support each other's Functions, it is less clear whether their local interaction in infected tissues can modulate the subsequent ability of migrating DC to induce T cell responses in draining lymph nodes. In this study, we report that NK cells are capable of inducing stable type 1-polarized "effector/memory" DC (DC1) that act as carriers of NK cell-derived Helper signals for the development of type 1 immune responses. NK cell-induced DC1 show a strongly elevated ability to produce IL-12p70 after subsequent CD40 ligand stimulation. NK-induced DC1 prime naive CD4+ Th cells for high levels of IFN-gamma, but low IL-4 production, and demonstrate a strongly enhanced ability to induce Ag-specific CD8+ T cell responses. Resting NK cells display stringent activation requirements to perform this novel, DC-mediated, "Helper" Function. Although their interaction with K562 cells results in effective target cell killing, the induction of DC1 requires a second NK cell-activating signal. Such costimulatory signal can be provided by type I IFNs, common mediators of antiviral responses. Therefore, in addition to their cytolytic Function, NK cells also have immunoregulatory activity, induced under more stringent conditions. The currently demonstrated Helper activity of NK cells may support the development of Th1- and CTL-dominated type 1 immunity against intracellular pathogens and may have implications for cancer immunotherapy.

Kurt Tobler - One of the best experts on this subject based on the ideXlab platform.

Enrico Maggi - One of the best experts on this subject based on the ideXlab platform.

  • Th2-like CD8+ T cells showing B cell Helper Function and reduced cytolytic activity in human immunodeficiency virus type 1 infection.
    Journal of Experimental Medicine, 1994
    Co-Authors: Enrico Maggi, Maria Grazia Giudizi, Roberta Biagiotti, Francesco Annunziato, Roberto Manetti, Marie-pierre Piccinni, Paola Parronchi, S. Sampognaro, L. Giannarini, Giuliano Zuccati
    Abstract:

    We analyzed at clonal level the Functional profile of circulating or skin-infiltrating T lymphocytes from two individuals infected with the human immunodeficiency virus type 1 (HIV-1), suffering from a Job's-like syndrome (eczematous dermatitis, recurrent skin and sinopulmonary infections, and hypergammaglobulinemia E) and showing virtually no circulating CD4+ T cells. Most of the CD3+ T cell clones generated from both patients were CD4- CD8+ TCR alpha beta +. The others were CD4- CD8- TCR alpha beta + which exhibited reduced mRNA expression for the CD8 molecule or no mRNA expression for either CD4 or CD8 molecules. The great majority of both CD4- CD8+ and CD4- CD8- did not produce interferon (IFN) gamma and exhibited reduced cytolytic activity. Rather, most of them produced large amounts of both interleukin (IL) 4 and IL-5 and provided B cell Helper Function for IgE synthesis. These data suggest that a switch of cytolytic CD8+ T cells showing a Th1-like cytokine secretion profile to cells that make Th2-type cytokines, exhibit reduced cytolytic potential, and provide B cell Helper Function can occur in the course of HIV-1 infection. These cells may contribute to the reduced defense against viral infections and intracellular parasites and account for the elevated IgE serum levels, eosinophilia, and the allergic-like clinical manifestations seen in a proportion of HIV-1-infected individuals.

  • in vitro infection with hiv enables human cd4 t cell clones to induce noncognate contact dependent polyclonal b cell activation
    Journal of Immunology, 1991
    Co-Authors: D Macchia, Enrico Maggi, Marie-pierre Piccinni, Paola Parronchi, C Simonelli, Marcello Mazzetti, Adriana Ravina, Domenico Milo, Sergio Romagnani
    Abstract:

    Eleven (nine CD4+ and two CD8+) protein purified derivative-specific and eight tetanus toxoid-specific T cell clones (TCC), established from the peripheral blood of healthy persons, were cocultured in vitro with irradiated mononuclear cells from patients infected by HIV in the presence of PHA and polybrene. Two weeks post-HIV exposure, all 17 CD4+, but neither of the two CD8+, TCC exhibited integration of HIV in their genoma, as detected by polymerase chain reaction analysis, and released HIV into their supernatants, as detected by measuring both reverse transcriptase activity and p24 Ag. When co-cultured with either autologous or allogeneic B cells, all CD4+ HIV-infected TCC induced the synthesis of extraordinarily high amounts of IgM, IgG, and IgA. In contrast, their noninfected counterparts could provide Helper Function for Ig synthesis by autologous B cells only in the presence of the specific Ag (or anti-CD3 antibody), and induced allogeneic B cells to synthesize Ig only upon stimulation with anti-CD3 antibody. The supernatants of HIV-infected TCC failed to stimulate Ig synthesis in B cells. More importantly, when HIV-infected clonal T blasts and B cells were cultured in different chambers separated by a millipore membrane, permeable to molecules but not to cells, Ig synthesis did not occur. The Ig synthesis induced by HIV-infected TCC was also markedly inhibited by the addition in culture of either anti-CD4 or anti-LFA-1 antibody. In contrast, HIV-infected TCC maintained their ability to provide Helper Function for Ig synthesis in the absence of any stimulus, even after fixation with p-formaldehyde. These data demonstrate that in vitro infection with HIV enables human T cells to stimulate Ig synthesis by B cells by an Ag-nonspecific, MHC-unrestricted, contact-dependent mechanism. This may explain, at least in part, the hypergammaglobulinemia and other phenomena related to polyclonal B cell activation frequently seen in HIV-infected persons.

  • accumulation of th 2 like Helper t cells in the conjunctiva of patients with vernal conjunctivitis
    Journal of Immunology, 1991
    Co-Authors: Enrico Maggi, Paola Parronchi, G. F. Del Prete, A. Tiri, C Simonelli, P Biswas, D Macchia, L Emmi, M De Carli, M Ricci
    Abstract:

    A total number of 132 T cell clones (TCC) were obtained by PHA-stimulation of single T cells from mononuclear cell suspensions of conjunctival flogistic infiltrates of three patients with vernal conjunctivitis (VC). The phenotype and Functional properties of these TCC were compared with those of 122 TCC contemporarily established from PB mononuclear cell suspensions of the same patients, 120 TCC established from lymph nodes of three patients with nonspecific hyperplastic lymphoadenitis and 159 TCC established from thyroid lymphocyte infiltrates of three patients with Graves' disease. The great majority of conjunctival TCC displayed the CD4+ CD8- phenotype (CD4/CD8 ratios ranging from 6.1 to 7.0), whereas the mean CD4/CD8 ratios for control TCC ranged from 0.9 to 2.4. After stimulation with either PHA or PMA plus anti-CD3 mAb, conjunctival TCC differed from control TCC for their ability to produce cytokines. In particular, a large number of conjunctival TCC produced IL-4, but no, or limited amounts of, IFN-gamma, whereas no difference was observed between conjunctival and control TCC with regard to the production of IL-2. The failure of IFN-gamma production by conjunctival TCC was apparently not caused by delay or block in cytokine production, but actually reflected the lack of IFN-gamma transcription. Virtually all conjunctival TCC able to produce IL-4, but not IFN-gamma, as well as most of those producing both cytokines, provided Helper Function for IgE synthesis in allogeneic normal B cells. The accumulation in the conjunctiva of patients with vernal conjunctivitis of CD4+ T cells that, apart from the production of IL-2, resembles murine Th2 cells for their profile of cytokine production and Helper Function suggests a possible role for these cells in the pathogenesis of the disease.

  • In vitro Infection with hiv of antigen-specific t cell clones derived from hiv-seronegative individuals. effects on cytokine production and Helper Function
    La Ricerca in Clinica E in Laboratorio, 1991
    Co-Authors: Donatella Macchia, Enrico Maggi, Marie-pierre Piccinni, Paola Parronchi, C Simonelli, P Biswas, Marcello Mazzetti, Adriana Ravina, Sergio Romagnani
    Abstract:

    Three human T cell clones (TCC) specific for purified protein derivative of Mycobacterium tuberculosis were incubated in the presence of polybrene and phytohemagglutinin with irradiated mononuclear cells from one individual exhibiting seropositivity for human immunodeficiency virus (HIV) and high levels of circulating p24 antigen. After three weeks, TCC showed HIV integration in their DNA, as shown by polymerase chain reaction analysis and Southern blot technique. All the three HIV-infected TCC maintained their ability to recognize the specific antigen, even if their proliferative ability was reduced. The ability of the HIV-infected TCC to produce IL-2, IL-4 and IFN-y in response to phorbol myristate acetate plus anti-CD3 monoclonal antibody was decreased, whereas their ability to produce TNF-α was unaffected or even enhanced. Two our. of the three HIV-infected TCC showed the ability to provide Helper Function for polyclonal immunoglobulin production when cocukured with autologous B cells in the absence of any stimulant. These data suggest that in vitro infection of normal human TCC may provide a useful model for the study of immunological alterations induced by HIV.

Yoshinaga Saeki - One of the best experts on this subject based on the ideXlab platform.