Inefficient response of T lymphocytes to glycosylphosphatidylinositol anchor-negative cells: implications for paroxysmal nocturnal hemoglobinuria
Inefficient response of T lymphocytes to glycosylphosphatidylinositol anchor-negative cells: implications for paroxysmal nocturnal hemoglobinuria
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DOI：
10.1182/blood-2002-06-1669
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发表时间：
2002-12-01
期刊：
影响因子：
20.3
通讯作者：
Kinoshita, T
中科院分区：
文献类型：
--
作者：
Murakami, Y;Kosaka, H;Kinoshita, T
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. (C) 2002 by The American Society of Hematology.
