Orthotopic Corneal Transplantation in Mice—evidence That the Immunogenetic Rules of Rejection Do Not Apply

Sonoda, Yoshito; Streilein, J. Wayne

doi:10.1097/00007890-199210000-00026

Cited by 257 publications

(212 citation statements)

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“…Transparency of the graft and degree of neovascularization in the graft and host tissue were recorded and scored to assess graft rejection according to the criteria listed in Table 1, which was put forward by previous researchers. [17][18] Mice with infection, hyphema, and cataracts were excluded, and the same quantity of recipient mice were recruited.…”

Section: Corneal Transplant (Penetrating Keratoplasty)mentioning

confidence: 99%

Pretreatment of Rapamycin Before Allogenic Corneal Transplant Promotes Graft Survival Through Increasing CD4+CD25+Foxp3+ Regulatory T Cells

Wang

Wang²,

Jia³

et al. 2012

Exp Clin Transplant

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Key words: Rapamycin, Regulatory T cells, Corneal transplantCorneal disease, one of the leading causes of blindness in China, 1 requires a corneal transplant to restore visual function in most cases. 2 Although immune privilege of corneal allografts endows a high success rate of corneal transplant than other solid-organ transplants, immunologic rejection remains a major cause of graft failure after corneal transplant. 3,4 Regulatory CD4 + CD25 + Foxp3 + T cells (Treg), an important regulator in maintaining immune homeostasis, play a crucial role in autoimmune diseases and tumors, and protect individuals from graft rejection. 5 However, Treg cells are present in low numbers under normal conditions, reported to be 5% to 10% of CD4 + T cells in mice and human blood, and have an anergic phenotype. 6 Therefore, enhancement of activated Treg cells may protect individuals from autoimmune diseases and graft rejection, just as previous studies have revealed. [7][8][9][10] Rapamycin, a novel macrolide immunosuppressive drug, has been reported to prevent clinical allograft rejections including corneal allografts. 11 Moreover, rapamycin allows expansion of CD4 + CD25 + Foxp3 + Treg in vitro and in vivo, 12-14 and CD4 + CD25 + Foxp3 + Treg converted by rapamycin has more-potent regulatory abilities. 15 It has been shown that adoptive transfer of CD4 + CD25 + Foxp3 + Treg expanded by rapamycin in vitro is capable of artIClE

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Section: Corneal Transplant (Penetrating Keratoplasty)mentioning

confidence: 99%

Pretreatment of Rapamycin Before Allogenic Corneal Transplant Promotes Graft Survival Through Increasing CD4+CD25+Foxp3+ Regulatory T Cells

Wang

Wang²,

Jia³

et al. 2012

Exp Clin Transplant

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“…The high acceptance rate of corneal transplants in both human and experimental animals is an expression of the capacity of immune privilege to reduce destructive immune responses [3,4].…”

Section: Introductionmentioning

confidence: 99%

A CIITA‐independent pathway that promotes expression of endogenous rather than exogenous peptides in immune‐privileged sites

et al. 2004

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A CIITA-independent pathway of MHC class II expression has been found in the eye and the brain, both immune-privileged sites. Although corneal endothelial cells were unable to express MHC class II in response to IFN-+ alone, these cells readily expressed MHC class II molecules via a CIITA-independent pathway when triggered by simultaneous exposure to IFN-+ and TNF- § . CIITA-independent expression of MHCclass II molecules enabled corneal endothelial cells to present cytosolic, but not endosomal, ovalbumin (OVA) to OVA-primed T cells. To determine whether CIITA-independent expression of MHC class II is relevant in vivo, minor H-only-incompatible corneal allografts prepared from CIITA knockout (KO) mice, MHC class II KO mice or wild-type donors were placed in eyes of normal mice. Cornea allografts from wild-type and CIITA KO mice suffered similar rejection fates, whereas far fewer class II-deficient corneas were rejected. In addition, MHC class II-bearing macrophages were observed in cuprizone-induced inflammatory and demyelinating brain lesions of CIITA KO mice. We conclude that class II expression via the CIITA-independent pathway enhances the vulnerability to rejection of corneal grafts expressing minor antigens. The potential relevance of CIITA-independent MHC class II expression at immune-privileged sites is discussed in relation to tolerance to strong autoantigens.

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“…Because both angiogenesis and lymphangiogenesis are involved in corneal allograft rejection, we determined the effects of treatment with soluble VEGFR2/Fc chimera protein on these processes after PKP (Sonoda and Streilein 1992). A significant reduction of corneal graft neovascularization was found in the sR2/Fc group, with angiogenesis and lymphangiogenesis being suppressed by 30% (p < 0.01) and 70% (p < 0.01), respectively, compared with the IgG/ Fc group ( Fig.…”

Section: Angiogenesis and Lymphangiogenesis After Corneal Transplantamentioning

confidence: 98%

“…Sutures were removed at 7 days after surgery. Postoperatively, the corneal grafts were assessed for opacity and neovascularization by using a scoring system that has been previously reported (Sonoda and Streilein 1992;Sano et al 1997).…”

Section: Full-thickness Corneal Transplantationmentioning

confidence: 99%

Suppression of Allograft Rejection with Soluble VEGF Receptor 2 Chimeric Protein in a Mouse Model of Corneal Transplantation

Hayashi

Usui

Yamagami

2016

Tohoku J. Exp. Med.

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When a transparent cornea becomes opaque due to infectious diseases, trauma, or ophthalmic surgery, the impaired cornea is replaced with a donor cornea to improve visual function. In this corneal transplantation, the graft survival rate is comparatively high, partly because of lacking vascular and lymphatic vessel in cornea. However, the transplanted corneas sometimes become opaque if allograft rejection occurs. Suppression of allograft rejection is critical for favorable outcomes of corneal transplantation. The essential effects of endogenous monomeric soluble vascular endothelial growth factor receptors (VEGFRs) 1 and 2 have been reported in corneal angiogenesis and lymphangiogenesis. This study investigated the effects of dimeric soluble VEGFR2/Fc chimera protein on corneal allograft rejection for future clinical application. Allogeneic full-thickness corneal transplantation was performed in C57BL/6 to BALB/c mice. The recipients were treated by intrastromal injection of soluble VEGFR1/Fc chimera (sR1/Fc group), soluble VEGFR2/Fc chimera (sR2/Fc group), or human IgG1/Fc protein (IgG/Fc group) at 0, 7, and 14 days after surgery. Both hemangiogenesis and lymphangiogenesis were significantly suppressed in the corneas of the sR2/Fc group compared with the IgG/Fc group. All grafts failed due to corneal wound rupture in the sR1/Fc group. In the sR2/Fc group, respective donor-derived MHC class II + /CD11c + cells and CD11b-positive macrophage infiltration were reduced in the DLNs and the corneas showing a negative delayed-type hypersensitivity, compared with the IgG/Fc group. Our findings demonstrate that soluble VEGFR2/Fc chimera protein efficiently suppresses corneal allo-rejection, while reducing hemangiogenesis and lymhangiogenesis, and immune-competent cell-trafficking and may be a powerful tool for corneal allograft survival.

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Orthotopic Corneal Transplantation in Mice—evidence That the Immunogenetic Rules of Rejection Do Not Apply

Cited by 257 publications

References 0 publications

Pretreatment of Rapamycin Before Allogenic Corneal Transplant Promotes Graft Survival Through Increasing CD4+CD25+Foxp3+ Regulatory T Cells

Pretreatment of Rapamycin Before Allogenic Corneal Transplant Promotes Graft Survival Through Increasing CD4+CD25+Foxp3+ Regulatory T Cells

A CIITA‐independent pathway that promotes expression of endogenous rather than exogenous peptides in immune‐privileged sites

Suppression of Allograft Rejection with Soluble VEGF Receptor 2 Chimeric Protein in a Mouse Model of Corneal Transplantation

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