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T-cell suppression by programmed cell death 1 ligand 1 on retinal pigment epithelium during inflammatory conditions.
Invest Ophthalmol Vis Sci. 2009 Jun; 50(6):2862-70.IO

Abstract

PURPOSE

To determine whether retinal pigment epithelial (RPE) cells can inhibit in vitro T-cell activation during inflammatory conditions.

METHODS

Primary cultured RPE cells were established from normal C57BL/6 mice. Target bystander T cells were established from normal splenic T cells with anti-CD3 antibodies. T-cell activation was assessed for proliferation by both examining [(3)H]-thymidine incorporation and the production of interferon (IFN)gamma or IL-17, as determined by ELISA. Expression of programed cell death 1 ligand 1 (PD-L1) on RPE or recombinant mouse IFNgamma-pretreated RPE cells was evaluated using oligonucleotide microarray, RT-PCR, immune staining, and flow cytometry. Expression of programed cell death 1 (PD-1)(+) on target T cells was evaluated by flow cytometry. Anti-mouse PD-L1 or PD-L2 neutralizing antibodies or target T cells from PD-1 knockout donors were used for the assay.

RESULTS

IFNgamma-pretreated RPE greatly suppressed activation of bystander T cells, especially the IFNgamma production by the target T cells (Th1 cells, but not Th17 cells) via direct cell contact. By examining cell surface candidate molecules, IFNgamma-pretreated RPE expressed much higher levels of PD-L1 compared with the control nontreated RPE. Although primary RPE did not express the costimulatory molecule, expression of the molecule was induced on the surface of IFNgamma-pretreated RPE. PD-L1(+) RPE in the presence of IFNgamma selectively suppressed PD-1(+) T-cell activation. IFNgamma-pretreated RPE in the presence of anti-PD-L1 neutralizing antibodies, but not anti-PD-L2, failed to suppress T-cell production of IFNgamma. In addition, these RPE cells failed to suppress the production of IFNgamma by CD4(+) T cells from PD-1 null donors.

CONCLUSIONS

Suppression of T-cell activation was obtained in cultures only when RPE expressed negative costimulators. Therefore, the authors propose that in vitro, Th1 cytokine-exposed ocular resident cells can express this molecule and it is this expression that causes the suppression of the bystander Th1-type cells.

Authors+Show Affiliations

Department of Ophthalmology & Visual Science, Tokyo Medical and Dental University Graduate School, Tokyo, Japan. sunaoph@tmd.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19182257

Citation

Sugita, Sunao, et al. "T-cell Suppression By Programmed Cell Death 1 Ligand 1 On Retinal Pigment Epithelium During Inflammatory Conditions." Investigative Ophthalmology & Visual Science, vol. 50, no. 6, 2009, pp. 2862-70.
Sugita S, Usui Y, Horie S, et al. T-cell suppression by programmed cell death 1 ligand 1 on retinal pigment epithelium during inflammatory conditions. Invest Ophthalmol Vis Sci. 2009;50(6):2862-70.
Sugita, S., Usui, Y., Horie, S., Futagami, Y., Aburatani, H., Okazaki, T., Honjo, T., Takeuchi, M., & Mochizuki, M. (2009). T-cell suppression by programmed cell death 1 ligand 1 on retinal pigment epithelium during inflammatory conditions. Investigative Ophthalmology & Visual Science, 50(6), 2862-70. https://doi.org/10.1167/iovs.08-2846
Sugita S, et al. T-cell Suppression By Programmed Cell Death 1 Ligand 1 On Retinal Pigment Epithelium During Inflammatory Conditions. Invest Ophthalmol Vis Sci. 2009;50(6):2862-70. PubMed PMID: 19182257.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - T-cell suppression by programmed cell death 1 ligand 1 on retinal pigment epithelium during inflammatory conditions. AU - Sugita,Sunao, AU - Usui,Yoshihiko, AU - Horie,Shintaro, AU - Futagami,Yuri, AU - Aburatani,Hiroyuki, AU - Okazaki,Taku, AU - Honjo,Tasuku, AU - Takeuchi,Masaru, AU - Mochizuki,Manabu, Y1 - 2009/01/31/ PY - 2009/2/3/entrez PY - 2009/2/3/pubmed PY - 2009/6/12/medline SP - 2862 EP - 70 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 50 IS - 6 N2 - PURPOSE: To determine whether retinal pigment epithelial (RPE) cells can inhibit in vitro T-cell activation during inflammatory conditions. METHODS: Primary cultured RPE cells were established from normal C57BL/6 mice. Target bystander T cells were established from normal splenic T cells with anti-CD3 antibodies. T-cell activation was assessed for proliferation by both examining [(3)H]-thymidine incorporation and the production of interferon (IFN)gamma or IL-17, as determined by ELISA. Expression of programed cell death 1 ligand 1 (PD-L1) on RPE or recombinant mouse IFNgamma-pretreated RPE cells was evaluated using oligonucleotide microarray, RT-PCR, immune staining, and flow cytometry. Expression of programed cell death 1 (PD-1)(+) on target T cells was evaluated by flow cytometry. Anti-mouse PD-L1 or PD-L2 neutralizing antibodies or target T cells from PD-1 knockout donors were used for the assay. RESULTS: IFNgamma-pretreated RPE greatly suppressed activation of bystander T cells, especially the IFNgamma production by the target T cells (Th1 cells, but not Th17 cells) via direct cell contact. By examining cell surface candidate molecules, IFNgamma-pretreated RPE expressed much higher levels of PD-L1 compared with the control nontreated RPE. Although primary RPE did not express the costimulatory molecule, expression of the molecule was induced on the surface of IFNgamma-pretreated RPE. PD-L1(+) RPE in the presence of IFNgamma selectively suppressed PD-1(+) T-cell activation. IFNgamma-pretreated RPE in the presence of anti-PD-L1 neutralizing antibodies, but not anti-PD-L2, failed to suppress T-cell production of IFNgamma. In addition, these RPE cells failed to suppress the production of IFNgamma by CD4(+) T cells from PD-1 null donors. CONCLUSIONS: Suppression of T-cell activation was obtained in cultures only when RPE expressed negative costimulators. Therefore, the authors propose that in vitro, Th1 cytokine-exposed ocular resident cells can express this molecule and it is this expression that causes the suppression of the bystander Th1-type cells. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/19182257/T_cell_suppression_by_programmed_cell_death_1_ligand_1_on_retinal_pigment_epithelium_during_inflammatory_conditions_ DB - PRIME DP - Unbound Medicine ER -