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Prepublished online as a Blood First Edition Paper on July 18, 2002; DOI 10.1182/blood-2002-06-1669.
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Blood, 1 December 2002, Vol. 100, No. 12, pp. 4116-4122
IMMUNOBIOLOGY
Inefficient response of T lymphocytes to
glycosylphosphatidylinositol anchor-negative cells: implications for
paroxysmal nocturnal hemoglobinuria
Yoshiko Murakami,
Hiroshi Kosaka,
Yusuke Maeda,
Jun-ichi Nishimura,
Norimitsu Inoue,
Kazuhito Ohishi,
Masaru Okabe,
Junji Takeda, and
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.
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.
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