PD-L1 expression on human ocular cells and its possible role in regulating immune-mediated ocular inflammation.
OBJECTIVE
To assess the expression of PD-L1 and PD-L2 on human ocular cells and their potential to regulate ocular inflammation.


METHODS
Five categories of human ocular cells were evaluated for PD-L1 and PD-L2 expression by RT-PCR and flow cytometry. Three normal eyes and an inflamed eye from a patient with sympathetic ophthalmia were examined by immunohistochemistry for in situ PD-L1 expression. The immunomodulatory functions of PD-L1 and PD-L2 were tested by coculturing untreated or IFN-gamma-pretreated ocular cells with activated human peripheral blood T cells for 48 hours and assessing T-cell production of IFN-gamma, TNF-alpha, IL-4, and IL-5 by ELISA and T-cell apoptosis by flow cytometry.


RESULTS
PD-L1 protein was expressed constitutively in 4 of 5 human ocular cell lines, and its expression was significantly upregulated after stimulation by IFN-gamma. Moreover, in situ expression of PD-L1 in inflamed ocular tissues was remarkably upregulated compared with normal eyes. Although PD-L2 expression was detectable by flow cytometry on 3 of 5 ocular cell lines, immunohistochemical staining did not show expression of PD-L2 on either normal or inflamed ocular tissues. IFN-gamma, TNF-alpha, and IL-5 production by activated T cells cocultured with ocular cells was significantly enhanced in the presence of anti-PD-L1 blocking antibody. However, ocular cell-expressed PD-L1 and PD-L2 did not induce T-cell apoptosis.


CONCLUSIONS
PD-L1 expressed on human ocular cells has a presumptive role in controlling ocular inflammation by inhibiting the production of proinflammatory cytokines and a Th2 cytokine by activated T cells. This may represent an important mechanism for maintaining immune privilege in the eye.
Yang
Wanhua
W
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9057, USA.
Li
Haochuan
H
Chen
Peter W
PW
Alizadeh
Hassan
H
He
Yuguang
Y
Hogan
R Nick
RN
Niederkorn
Jerry Y
JY
D000869:Anterior Eye Segment / Q000166:cytology / Q000378:metabolism*; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D060890:B7-H1 Antigen; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D009879:Ophthalmia, Sympathetic / Q000276:immunology*; D061027:Programmed Cell Death 1 Ligand 2 Protein; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D012333:RNA, Messenger