Targeting NF‐κB c‐Rel in regulatory T cells to treat corneal transplantation rejection

The eye is provided with immune protection against pathogens in a manner that greatly reduces the threat of inflammation-induced vision loss. Immune-mediated inflammation and allograft rejection are greatly reduced in the eye, a phenomenon called ‘immune privilege’. Corneal tissue has inherent immune privilege properties with underlying three mechanisms: (1) anatomical, cellular, and molecular barriers in the cornea; (2) an immunosuppressive microenvironment; and (3) tolerance related to regulatory T cells and anterior chamber-associated immune deviation. This review describes the molecular mechanisms of the immunosuppressive microenvironment and regulatory T cells in the cornea that have been elucidated from animal models of ocular inflammation, especially those involving corneal transplantation, it also provides an update on immune checkpoint molecules in corneal and systemic immune regulation, and its relevance for dry eye associated with checkpoint inhibitor therapy.

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A New Immunotherapy Using Regulatory T-Cells for High-Risk Corneal Transplantation

Juntendo Medical Journal ◽

10.14789/jmj.63.2 ◽

2017 ◽

Vol 63 (1) ◽

pp. 2-7 ◽

Cited By ~ 1

Author(s):

TAKENORI INOMATA

Keyword(s):

T Cells ◽

High Risk ◽

Regulatory T Cells ◽

Corneal Transplantation

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The Balance of Th1/Th2 and LAP+Tregs/Th17 Cells Is Crucial for Graft Survival in Allogeneic Corneal Transplantation

Journal of Ophthalmology ◽

10.1155/2018/5404989 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Shang Li ◽

Jing Yu ◽

Chungang Guo ◽

Ying Jie ◽

Zhiqiang Pan

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Aqueous Humor ◽

Allograft Rejection ◽

Corneal Transplantation ◽

Allograft Survival ◽

Survival Group ◽

Corneal Allograft ◽

Group 3 ◽

Corneal Allograft Rejection

Purpose. CD4+LAP+ T cells are newly discovered regulatory T cells (Tregs). The aim of this study is to investigate the balance of Th1/Th2 and LAP+Tregs/Th17 in mice after allogeneic corneal transplantation. Methods. A total of 65 mice received orthotopic penetrating transplantation. According to the survival scores of the grafts, the mice were divided into the rejection group and the survival group 3 weeks after transplantation. Th1, Th2, Th17, and regulatory T cells in the ipsilateral drainage lymph nodes and spleens were measured with flow cytometry. The related cytokines in aqueous humor were also analyzed. Results. The frequencies of Foxp3+Tregs, GARP+Tregs, and LAP+Tregs in the survival group were significantly higher than those in the rejection group. And the expression trend of CD4+LAP+ T cells and CD4+GARP+ T cells was consistent. The level of IFN-γ, TNF, IL-6, and IL-17A markedly increased in aqueous humor during corneal allograft rejection. The ratio of Th1/Th2 and Th17/LAP+Tregs significantly increased in the rejection group at the 3rd week after corneal transplantation. Conclusion. LAP+Tregs might be regarded as substitute for Foxp3+Tregs. The balance of Th1/Th2 and LAP+Tregs/Th17 is crucial for corneal allograft survival.

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Multiplex immunofluorescence of spatial distribution of infiltrating T cells in different regions of hepatic lobules during liver transplantation rejection

10.21203/rs.3.rs-508924/v1 ◽

2021 ◽

Author(s):

Shipeng Li ◽

Guangpeng Zhou ◽

Jie Sun ◽

Bin Cui ◽

Haiming Zhang ◽

...

Keyword(s):

Liver Transplantation ◽

T Cells ◽

Spatial Distribution ◽

Regulatory T Cells ◽

Acute Rejection ◽

Cd8 T Cells ◽

Immune Cells ◽

Cd4 T Cells ◽

Rejection Level ◽

Transplantation Rejection

Abstract It is still unclear whether there are differences in the types and functional status of immune cells in different areas of the liver lobules after liver transplantation rejection. The composition of infiltrating T cells in liver allografts during liver transplantation rejection is unclear and difficult to visualize on the same biopsy slide. We used multiplex immunofluorescence assays to study the spatial distribution of various types of infiltrating T cells in different areas of the liver lobules after liver transplantation. In the same area of the hepatic lobules, the percentage of CD4 + T cells, CD8 + T cells and regulatory T cells (Tregs) in the acute rejection group was higher than that in the nonacute rejection and normal groups. Within all three groups, the percentage of CD4 + T cells, CD8 + T cells and Tregs from the periportal to perivenous zones was increased first and then decreased. The percentage of CD8 + T cells increased gradually from the periportal to perivenous zones, the percentage of CD8 + T cells in perivenous zone was higher than in the transitional and periportal zones in the rejection group. In conclusion, the percentage of CD8 + T cells in different regions of liver lobules is closely related to rejection level after liver transplantation. Acute liver transplantation rejection may occur when the percentage of CD8 + T cells in the perivenous zone increases. Although the percentage of regional CD4 + T could not reflect the rejection level, but the number of CD4 + and CD8 + T cells in different regions was closely related to the rejection level.

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