Human retinal pigment epithelial cell-induced apoptosis in activated T cells.
OBJECTIVE
The immune privilege of the eye has been thought to be dependent on physical barriers and absence of lymphatic vessels. However, the immune privilege may also involve active immunologic processes, as recent studies have indicated. The purpose of the present study was to investigate whether human retinal pigment epithelial (RPE) cells can induce apoptosis in activated T cells.


METHODS
Fas ligand (FasL) expression was detected by flow cytometry and immunohistochemistry. Cultured RPE cells were cocultured with T-cell lines and peripheral blood lymphocytes for 6 hours to 2 days. Induction of apoptosis was detected by 7-amino-actinomycin D and annexin V staining.


RESULTS
Retinal pigment epithelial cells expressed FasL and induced apoptosis in activated Fas+ T cells. Blocking of Fas-FasL interaction with antibody strongly inhibited RPE-mediated T-cell apoptosis. Retinal pigment epithelial cells induced apoptosis in several activated T-cell populations and T-cell lines, including T-cell antigen receptor (TCR)-CD3-negative T-cell lines. In contrast, RPE cells induced little or no apoptosis in resting peripheral T cells. Major histocompatibility complex (MHC) class II monoclonal antibodies, which block alloactivation, had no inhibitory effect on RPE-mediated T-cell apoptotic responses in MHC class II-specific CD4+ T-cell lines.


CONCLUSIONS
Retinal pigment epithelial cells express FasL and induce TCR-independent apoptosis in activated human T cells through Fas-FasL interaction. Retinal pigment epithelial cells may constitute an immunologic functional barrier against potentially harmful T cells.
Jørgensen
A
A
Institute of Medical Anatomy Section A, University of Copenhagen, Denmark.
Wiencke
A K
AK
la Cour
M
M
Kaestel
C G
CG
Madsen
H O
HO
Hamann
S
S
Lui
G M
GM
Scherfig
E
E
Prause
J U
JU
Svejgaard
A
A
Odum
N
N
Nissen
M H
MH
Röpke
C
C
D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D008213:Lymphocyte Activation / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D019014:fas Receptor / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor