Vulnerability of allogeneic retinal pigment epithelium to immune T-cell-mediated damage in vivo and in vitro.
OBJECTIVE
Because retinal pigment epithelium (RPE) constitutively expresses class I major histocompatibility complex (MHC) molecules, and CD95 ligand and secretes immunosuppressive factors, the vulnerability of these cells to attack by immune T cells is open to question. This study was conducted to determine the vulnerability of allogeneic RPE to damage by specifically sensitized T cells, both in vivo within the subretinal space, and in vitro.


METHODS
BALB/c lymphocytes presensitized to C57BL/6 antigens were injected into the subretinal space of eyes of C57BL/6 and gld/gld mice, and the eyes were examined clinically and histologically. RPE eyecups were produced from mouse eyes by removing the anterior segment and neuronal retina, leaving an intact monolayer of RPE. Sensitized BALB/c lymphocytes were placed in the RPE eyecup and incubated for 4 hours. The RPE layer of the eyecups was assessed by confocal microscopy for viability, after staining with propidium iodide and acridine orange.


RESULTS
Eyes that received T cells sensitized to C57BL/6 antigens displayed a circumscribed patch of persistent choroidal "whitening" clinically and a disrupted RPE cell layer histologically at the injection site at 5 days after injection. By 14 days, only RPE cells at the injection site were lost. RPE in eyecup preparations was relatively resistant in vitro to cytolysis by sensitized T cells, whether the eyecups were obtained from CD95-deficient or wild-type mice.


CONCLUSIONS
RPE monolayers, both in vivo and in vitro, are relatively resistant to immune-mediated attack by specifically sensitized T cells. This relative lack of vulnerability is independent of the expression of CD95 ligand by target RPE cells and implies that immune barriers to acceptance of allogeneic RPE transplants may be less than if transplanted cells are from nonocular tissues.
Zamiri
Parisa
P
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Zhang
Qiang
Q
Streilein
J Wayne
JW
D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010857:Pigment Epithelium of Eye / Q000276:immunology*; D012160:Retina / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins