Inefficient response of T lymphocytes to glycosylphosphatidylinositol anchor–negative cells: implications for paroxysmal nocturnal hemoglobinuria

DOI PDF 被引用文献24件
  • Yoshiko Murakami
    From the Department of Immunoregulation, Research Institute for Microbial Diseases, Department of Experimental Genome Research, Genome Information Research Center, and Departments of Dermatology and Environmental Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Hiroshi Kosaka
    From the Department of Immunoregulation, Research Institute for Microbial Diseases, Department of Experimental Genome Research, Genome Information Research Center, and Departments of Dermatology and Environmental Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Yusuke Maeda
    From the Department of Immunoregulation, Research Institute for Microbial Diseases, Department of Experimental Genome Research, Genome Information Research Center, and Departments of Dermatology and Environmental Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Jun-ichi Nishimura
    From the Department of Immunoregulation, Research Institute for Microbial Diseases, Department of Experimental Genome Research, Genome Information Research Center, and Departments of Dermatology and Environmental Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Norimitsu Inoue
    From the Department of Immunoregulation, Research Institute for Microbial Diseases, Department of Experimental Genome Research, Genome Information Research Center, and Departments of Dermatology and Environmental Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Kazuhito Ohishi
    From the Department of Immunoregulation, Research Institute for Microbial Diseases, Department of Experimental Genome Research, Genome Information Research Center, and Departments of Dermatology and Environmental Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Masaru Okabe
    From the Department of Immunoregulation, Research Institute for Microbial Diseases, Department of Experimental Genome Research, Genome Information Research Center, and Departments of Dermatology and Environmental Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Junji Takeda
    From the Department of Immunoregulation, Research Institute for Microbial Diseases, Department of Experimental Genome Research, Genome Information Research Center, and Departments of Dermatology and Environmental Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Taroh Kinoshita
    From the Department of Immunoregulation, Research Institute for Microbial Diseases, Department of Experimental Genome Research, Genome Information Research Center, and Departments of Dermatology and Environmental Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.

抄録

<jats:p>Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic stem cell disorder in which clonal cells defective in glycosylphosphatidylinositol (GPI) biosynthesis are expanded, leading to complement-mediated hemolysis. PNH is often associated with bone marrow suppressive conditions, such as aplastic anemia. One hypothetical mechanism for the clonal expansion of GPI−cells in PNH is that the mutant cells escape attack by autoreactive cytotoxic cells that are thought to be responsible for aplastic anemia. Here we studied 2 model systems. First, we made pairs of GPI+ and GPI− EL4 cells that expressed major histocompatibility complex (MHC) class II molecules and various types of ovalbumin. When the GPI-anchored form of ovalbumin was expressed on GPI+ and GPI− cells, only the GPI+cells presented ovalbumin to ovalbumin-specific CD4+ T cells, indicating that if a putative autoantigen recognized by cytotoxic cells is a GPI-anchored protein, GPI− cells are less sensitive to cytotoxic cells. Second, antigen-specific as well as alloreactive CD4+ T cells responded less efficiently to GPI− than GPI+ cells in proliferation assays. In vivo, when GPI− and GPI+ fetal liver cells, and CD4+ T cells alloreactive to them, were cotransplanted into irradiated hosts, the contribution of GPI− cells in peripheral blood cells was significantly higher than that of GPI+ cells. The results obtained with the second model suggest that certain GPI-anchored protein on target cells is important for recognition by T cells. These results provide the first experimental evidence for the hypothesis that GPI− cells escape from immunologic attack.</jats:p>

収録刊行物

  • Blood

    Blood 100 (12), 4116-4122, 2002-12-01

    American Society of Hematology

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