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*
Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114;
Core Research and Evolutional Science and Technology Project and Department of Molecular Immunology, Chiba University, Chiba, Japan;
Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115; and
Department of Ophthalmology, Kyushu University School of Medicine, Fukuoka, Japan
BALB/c mice that tolerate the allogeneic grafts develop
allogeneic-specific anterior chamber-associated immune deviation.
Because CD1d-reactive NKT cells are essential for anterior
chamber-associated immune deviation, we postulated that the survival of
C57BL/6 (B6) cornea graft in BALB/c mice was also dependent on
CD1d-reactive NKT cells. The B6 corneal graft rejection rate in BALB/c
vs J
281 knockout (KO) mice, which lack NKT cells, was
measured. While there were no difference in the early phase of
rejection, the survival rates at 12 wk after grafting for BALB/c and
J281 KO mice were 50 and 0%, respectively. Because anti-CD1d
mAb abrogated the corneal graft survival in the wild-type mice we
concluded that CD1d-reactive NKT cells were essential for graft
survival. Moreover, allospecific T regulatory (Tr) cells correlated
with acceptance of B6 grafts in BALB/c mice, and the adoptive transfer
of these allospecific Tr cells to J281 KO mice allowed a 50%
survival rate of B6 cornea grafts. In conclusion, CD1d-reactive NKT
cells are required for induction of allospecific Tr cells and are
essential for survival of corneal allografts. Mechanisms that
contribute to cornea graft acceptance may lead to new therapies for
improvement in graft survival in high-risk corneas and other
transplanted tissues and grafts.
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