title: Inefficient response of T lymphocytes to glycosylphosphatidylinositol anchor-negative cells: implications for paroxysmal nocturnal hemoglobinuria.
abstract: 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.
authors.affiliation: Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Murakami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kosaka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Maeda
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Nishimura
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Inoue
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Ohishi
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
authors.forename: Junji
authors.initials: J
authors.lastname: Takeda
authors.forename: Taroh
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D002999:Clone Cells / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D017261:Glycosylphosphatidylinositols / Q000032:analysis / Q000172:deficiency / Q000276:immunology*; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology* / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D039902:Multipotent Stem Cells / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D017261:Glycosylphosphatidylinositols; D000949:Histocompatibility Antigens Class II