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Kazumi Tanaka, Koh-hei Sonoda, J. Wayne Streilein; Acute Rejection of Orthotopic Corneal Xenografts in Mice Depends on CD4+ T Cells and Self-Antigen–Presenting Cells. Invest. Ophthalmol. Vis. Sci. 2001;42(12):2878-2884.
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purpose. Guinea pig corneal xenografts have been reported to be rejected acutely
in eyes of normal adult mice. Rejection of this type is independent of
xenoreactive antibodies, and mice deficient in CD8+ and NK
T cells are unable to reject guinea pig corneal grafts acutely.
Therefore, a study was conducted to determine the extent and manner by
which CD4+ T cells are responsible for rejection of
orthotopic corneal xenografts.
methods. Xenogeneic corneas were prepared from eyes of normal guinea pigs and
grafted orthotopically into normal eyes of C57BL/6 mice, class II major
histocompatibility complex (MHC) knockout (KO) mice, and class II MHC
KO mice reconstituted with syngeneic (C57BL/6) CD4+ T cells
and/or bone marrow cells. Graft survival was assessed clinically, and
success of cellular reconstitution was assayed using flow cytometric
analysis of peripheral blood leukocytes. T cells from rejector mice
were analyzed for proliferative responses to guinea pig xenoantigens in
results. Median survival times (MST) of corneal xenografts in MHC class II KO
mice was significantly delayed (31 days) compared with grafts in
wild-type C57BL/6 eyes (9 days). Acute rejection was restored almost
completely when MHC class II KO mice were reconstituted simultaneously
with C57BL/6 bone marrow and CD4+ T cells, but not when the
KO mice were reconstituted with either CD4+ T cells or bone
marrow cells alone. Mice that rejected guinea pig corneas possessed
only CD4+ T cells capable of responding to guinea pig
xenoantigens in vitro.
conclusions. Acute rejection of orthotopic corneal xenografts in mice is mediated by
CD4+ T cells that detect guinea pig xenoantigens that are
presented on MHC class II+ syngeneic antigen-presenting
cells. These results strongly suggest that rejection occurs exclusively
through the indirect pathway of T-cell
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