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Galectin-9-mediated protection from allo-specific T cells as a mechanism of immune privilege of corneal allografts.

Shimmura-Tomita M, Wang M, Taniguchi H, Akiba H, Yagita H, Hori J - PLoS ONE (2013)

Bottom Line: The eye is an immune-privileged organ, and corneal transplantation is therefore one of the most successful organ transplantation.T-cell immunoglobulin and mucin domain (Tim)-3 is a regulatory molecule for T-cell function, and galectin (Gal)-9 is a Tim-3 ligand.Blockade of Tim-3 or Gal-9 did not abolish anterior chamber-associated immune deviation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Nippon Medical School, Tokyo, Japan. machiko@jichi.ac.jp

ABSTRACT
The eye is an immune-privileged organ, and corneal transplantation is therefore one of the most successful organ transplantation. The immunosuppressive intraocular microenvironment is known as one of the mechanisms underlying immune privilege in the eye. T-cell immunoglobulin and mucin domain (Tim)-3 is a regulatory molecule for T-cell function, and galectin (Gal)-9 is a Tim-3 ligand. We investigated the role of this pathway in establishing the immune-privileged status of corneal allografts in mice. Gal-9 is constitutively expressed on the corneal epithelium, endothelium and iris-ciliary body in normal mouse eyes and eyes bearing surviving allografts, and Tim-3 was expressed on CD8 T cells infiltrating the allografts. Allograft survival in recipients treated with anti-Tim-3 monoclonal antibody (mAb) or anti-Gal-9 mAb was significantly shorter than that in control recipients. In vitro, destruction of corneal endothelial cells by allo-reactive T cells was enhanced when the cornea was pretreated with anti-Gal-9 mAb. Blockade of Tim-3 or Gal-9 did not abolish anterior chamber-associated immune deviation. We propose that constitutive expression of Gal-9 plays an immunosuppressive role in corneal allografts. Gal-9 expressed on corneal endothelial cells protects them from destruction by allo-reactive T cells within the cornea.

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Expression of Tim-3 and Gal-9 in normal eye tissue.(A) mRNA was extracted from freshly isolated cornea, iris-ciliary body, and neural retina of normal mouse eyes, and then reverse transcribed and amplified by PCR. PCR products were electrophoresed in 2% agarose gel and visualized by ethidium bromide staining. (B) Section of normal mouse cornea was stained using hematoxylin and eosin (HE). (C) Section of normal mouse iris-ciliary body was stained using HE. (D and F) Cryostat sections were stained with anti-Gal-9 mAb followed by FITC-conjugated anti-rat IgG (green). Nuclei were stained with PI (red). (E and G) Cryostat sections were stained with biotinylated anti-Tim-3 Ab followed by streptavidin-FITC (green). Nuclei were stained with DAPI (blue). Ced, corneal endothelium; Cst, corneal stroma; and Cep, corneal epithelium. Original magnification, ×40.
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pone-0063620-g001: Expression of Tim-3 and Gal-9 in normal eye tissue.(A) mRNA was extracted from freshly isolated cornea, iris-ciliary body, and neural retina of normal mouse eyes, and then reverse transcribed and amplified by PCR. PCR products were electrophoresed in 2% agarose gel and visualized by ethidium bromide staining. (B) Section of normal mouse cornea was stained using hematoxylin and eosin (HE). (C) Section of normal mouse iris-ciliary body was stained using HE. (D and F) Cryostat sections were stained with anti-Gal-9 mAb followed by FITC-conjugated anti-rat IgG (green). Nuclei were stained with PI (red). (E and G) Cryostat sections were stained with biotinylated anti-Tim-3 Ab followed by streptavidin-FITC (green). Nuclei were stained with DAPI (blue). Ced, corneal endothelium; Cst, corneal stroma; and Cep, corneal epithelium. Original magnification, ×40.

Mentions: Gal-9 mRNA was strongly expressed in freshly isolated cornea, iris-ciliary body, and the neural retina according to RT-PCR (Fig. 1A). Normal mouse cornea and iris-ciliary body with HE staining were showed in Fig. 1B, C. Immunofluorescent staining indicated that the expression of Gal-9 was localized to corneal epithelium and endothelial cells, but was absent in the corneal stroma (Fig.1D). Gal-9 protein was also expressed in the iris-ciliary body of normal mouse eyes (Fig.1F). RT-PCR revealed that Tim-3 mRNA was expressed in freshly isolated cornea and neural retina, and weakly expressed in the iris-ciliary body of normal mouse eyes (Fig. 1A). However, the expression of Tim-3 protein was not found by immunofluorescent staining in normal cornea or the iris-ciliary body (Fig.1E, G).


Galectin-9-mediated protection from allo-specific T cells as a mechanism of immune privilege of corneal allografts.

Shimmura-Tomita M, Wang M, Taniguchi H, Akiba H, Yagita H, Hori J - PLoS ONE (2013)

Expression of Tim-3 and Gal-9 in normal eye tissue.(A) mRNA was extracted from freshly isolated cornea, iris-ciliary body, and neural retina of normal mouse eyes, and then reverse transcribed and amplified by PCR. PCR products were electrophoresed in 2% agarose gel and visualized by ethidium bromide staining. (B) Section of normal mouse cornea was stained using hematoxylin and eosin (HE). (C) Section of normal mouse iris-ciliary body was stained using HE. (D and F) Cryostat sections were stained with anti-Gal-9 mAb followed by FITC-conjugated anti-rat IgG (green). Nuclei were stained with PI (red). (E and G) Cryostat sections were stained with biotinylated anti-Tim-3 Ab followed by streptavidin-FITC (green). Nuclei were stained with DAPI (blue). Ced, corneal endothelium; Cst, corneal stroma; and Cep, corneal epithelium. Original magnification, ×40.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3646846&req=5

pone-0063620-g001: Expression of Tim-3 and Gal-9 in normal eye tissue.(A) mRNA was extracted from freshly isolated cornea, iris-ciliary body, and neural retina of normal mouse eyes, and then reverse transcribed and amplified by PCR. PCR products were electrophoresed in 2% agarose gel and visualized by ethidium bromide staining. (B) Section of normal mouse cornea was stained using hematoxylin and eosin (HE). (C) Section of normal mouse iris-ciliary body was stained using HE. (D and F) Cryostat sections were stained with anti-Gal-9 mAb followed by FITC-conjugated anti-rat IgG (green). Nuclei were stained with PI (red). (E and G) Cryostat sections were stained with biotinylated anti-Tim-3 Ab followed by streptavidin-FITC (green). Nuclei were stained with DAPI (blue). Ced, corneal endothelium; Cst, corneal stroma; and Cep, corneal epithelium. Original magnification, ×40.
Mentions: Gal-9 mRNA was strongly expressed in freshly isolated cornea, iris-ciliary body, and the neural retina according to RT-PCR (Fig. 1A). Normal mouse cornea and iris-ciliary body with HE staining were showed in Fig. 1B, C. Immunofluorescent staining indicated that the expression of Gal-9 was localized to corneal epithelium and endothelial cells, but was absent in the corneal stroma (Fig.1D). Gal-9 protein was also expressed in the iris-ciliary body of normal mouse eyes (Fig.1F). RT-PCR revealed that Tim-3 mRNA was expressed in freshly isolated cornea and neural retina, and weakly expressed in the iris-ciliary body of normal mouse eyes (Fig. 1A). However, the expression of Tim-3 protein was not found by immunofluorescent staining in normal cornea or the iris-ciliary body (Fig.1E, G).

Bottom Line: The eye is an immune-privileged organ, and corneal transplantation is therefore one of the most successful organ transplantation.T-cell immunoglobulin and mucin domain (Tim)-3 is a regulatory molecule for T-cell function, and galectin (Gal)-9 is a Tim-3 ligand.Blockade of Tim-3 or Gal-9 did not abolish anterior chamber-associated immune deviation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Nippon Medical School, Tokyo, Japan. machiko@jichi.ac.jp

ABSTRACT
The eye is an immune-privileged organ, and corneal transplantation is therefore one of the most successful organ transplantation. The immunosuppressive intraocular microenvironment is known as one of the mechanisms underlying immune privilege in the eye. T-cell immunoglobulin and mucin domain (Tim)-3 is a regulatory molecule for T-cell function, and galectin (Gal)-9 is a Tim-3 ligand. We investigated the role of this pathway in establishing the immune-privileged status of corneal allografts in mice. Gal-9 is constitutively expressed on the corneal epithelium, endothelium and iris-ciliary body in normal mouse eyes and eyes bearing surviving allografts, and Tim-3 was expressed on CD8 T cells infiltrating the allografts. Allograft survival in recipients treated with anti-Tim-3 monoclonal antibody (mAb) or anti-Gal-9 mAb was significantly shorter than that in control recipients. In vitro, destruction of corneal endothelial cells by allo-reactive T cells was enhanced when the cornea was pretreated with anti-Gal-9 mAb. Blockade of Tim-3 or Gal-9 did not abolish anterior chamber-associated immune deviation. We propose that constitutive expression of Gal-9 plays an immunosuppressive role in corneal allografts. Gal-9 expressed on corneal endothelial cells protects them from destruction by allo-reactive T cells within the cornea.

Show MeSH
Related in: MedlinePlus