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Hartmut Wenkel, J. Wayne Streilein; Evidence that Retinal Pigment Epithelium Functions as an Immune-Privileged Tissue. Invest. Ophthalmol. Vis. Sci. 2000;41(11):3467-3473.
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purpose. Tissues derived from immune-privileged sites sometimes possess special
characteristics that promote their own survival when transplanted to a
nonprivileged site. This study was undertaken to evaluate whether
retinal pigment epithelium (RPE) behaves as an immune-privileged tissue
when transplanted extraocularly.
methods. RPE grafts were prepared from eyes of neonatal C57BL/6 or C57BL/6 gld/gld (deficient in CD95 ligand expression) mice.
These grafts (or conjunctival grafts as positive controls) were
transplanted into the anterior chamber, the subretinal space, the
subconjunctival space, and underneath the kidney capsule of
histoincompatible BALB/c mice. Transplant survival was evaluated by
histology at selected time points after engraftment. Recipients were
tested for acquisition of C57BL/6-specific delayed-type
hypersensitivity (DH) and for the ability to suppress DH.
results. Allogeneic neonatal RPE grafts from normal donors showed significantly
enhanced survival at all graft sites compared with conjunctival grafts.
However, allogeneic RPE cell grafts from gld/gld mice
were rapidly rejected after transplantation beneath the kidney capsule.
Allogeneic RPE grafts placed in extraocular sites induced systemic DH
directed at donor alloantigens, whereas RPE allografts placed
intraocularly induced suppression of systemic DH.
conclusions. Allogeneic neonatal RPE grafts, through constitutive expression of CD95
ligand, promote their own survival at heterotopic sites. Paradoxically,
these grafts also display immunogenicity. Thus, neonatal RPE tissue
owes its immune privilege to the capacity to prevent immune rejection
rather than to inhibit sensitization.
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