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Kazumi Tanaka, Jun Yamada, J. Wayne Streilein; Xenoreactive CD4+ T Cells and Acute Rejection of Orthotopic Guinea Pig Corneas in Mice. Invest. Ophthalmol. Vis. Sci. 2000;41(7):1827-1832.
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purpose. To explore immunologic issues involved in orthotopic corneal
xenotransplantation in a discordant combination using guinea pigs as
donors and mice as recipients.
methods. Two-millimeter-diameter guinea pig corneal buttons were transplanted
into 1.5-mm-diameter graft beds on mouse corneas using 12 interrupted
sutures. Eyelids were maintained occluded with tarsorrhaphy except at
the times of clinical inspection. Grafts were considered to be rejected
when the pupil margin was not visible clearly through the graft by
results. Guinea pig corneas protected from desiccation by persistent
tarsorrhaphy survived indefinitely in the eyes of C.B-17SCID mice but
were rejected acutely (but not hyperacutely) in eyes of normal BALB/c
and C57BL/6 mice (median survival times, MST, 16 and 10 days,
respectively). Graft survival was not extended in mice deficient in μ
heavy chain or β-2 microglobulin genes, slightly extended in mice
deficient in the C3 gene (MST of 21 versus 17 days) and greatly
extended in mice deficient in the CD4 gene (MST of 26 versus 9 days).
Reconstitution of CD4 knock-out (KO) mice with CD4+ T cells
promoted acute rejection of corneal xenografts.
conclusions. Hyperacute rejection does not occur in guinea pig corneal xenografts in
mouse eyes, indicating that corneal xenografts are less vulnerable to
this type of rejection than other solid tissue xenografts.
CD4+ T cells are the primary mediators of acute graft
rejection, although complement may contribute in a minor way. Neither
antibodies nor CD8+ T cells participate in acute graft
rejection. Because guinea pig cornea grafts in eyes of CD4KO mice are
rejected in a delayed fashion, other innate and/or adaptive immune
effectors must also be able to cause rejection of orthotopic corneal
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