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Jun Yamada, Iwao Kurimoto, J. Wayne Streilein; Role of CD4+ T Cells in Immunobiology of Orthotopic Corneal Transplants in Mice. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2614-2621.
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purpose. To determine, with the use of mice genetically deficient in expression
of CD4 or CD8 molecules, which T cells are responsible for rejection of
orthotopic corneal allografts in mice.
methods. Corneas were prepared from major histocompatibility complex (MHC)–only
incompatible, minor histocompatibility (H)–only incompatible, and
MHC-plus-minor H incompatible donors and grafted orthotopically to eyes
of CD4 knockout (KO), CD8KO, and wild-type control mice. Graft survival
patterns were assessed clinically and compared. Mice that retained
healthy corneal allografts beyond 8 weeks were evaluated for evidence
of donor-specific tolerance and anterior-chamber–associated immune
deviation (ACAID) using local adoptive transfer reactions and challenge
with orthotopic skin allografts.
results. Corneas grafted to CD8KO mice were rejected with an incidence and tempo
indistinguishable from that in wild-type control animals. By contrast,
MHC-only, and minor-H–only incompatible corneal grafts survived
indefinitely in eyes of CD4KO mice. Approximately 50% of corneal
grafts that confronted CD4KO recipients with both MHC and minor H
alloantigens experienced delayed rejection, whereas similar grafts in
wild-type recipients were rejected acutely. CD4KO mice with
long-accepted grafts displayed neither donor-specific ACAID nor
conclusions. CD8+ T cells play little or no role in acute rejection of
orthotopic corneal allografts. Instead, acute rejection is mediated
almost exclusively by CD4+ T cells. Moreover, when corneal
allografts survive for 8 weeks without acute rejection,
CD4+ T cells promote donor-specific ACAID thereby insuring
long-term graft acceptance.
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