Corneal infiltrating natural killer cell phenotypes in corneal rejection

Session Details

Session Title: Cornea & Miscellaneous
Session Date/Time: Friday 15/02/2019 | 10:30-12:30
Paper Time: 11:00
Venue: Room MC3

First Author: F.Esen TURKEY
Co Author(s): S. Genç  V. Aykut  R. Karadag  G. Deniz  H. Oguz  E. Cetin  

Abstract Details

Purpose:

Corneal rejection is an important factor limiting success of corneal transplantation. Natural killer (NK) cells are innate lymphoid cells that have crucial cytotoxic and regulatory roles trough cytokine and chemokines. NK cells can be divided into 3 subsets based on expression density of CD56: cytokine-secreting CD16-CD56bright/dim and cytotoxic CD16brightCD56dim and CD16brightCD56- subsets. PD-1 is an immune checkpoint receptor regulating lymphocyte function that is a component of ocular immune-privilege. PD-1+ NK cells are functionally exhausted, and exhibit reduced cytotoxic and cytokine secreting capacity. The aim of this study was to define NK cell subgroups and their PD-1 expression in corneal rejection

Setting:

University Hospital Ophthalmology Clinic and Immunology Laboratory

Methods:

Corneal tissues and aquaous humor samples were taken from seven chronic corneal rejection patients. Blood samples were also obtained from 12 healthy donors to serve as control group. The corneal infiltrating lymphocytes were isolated from the corneal tissue with gentle MACS dissociator (Miltenyi Biotec, Cologne, Germany). Cells were stained with CD3-FITC, anti-CD16-Pacific blue, anti-CD56-PerCP and PD-1-APC-Cy7 monoclonal antibodies and analyzed by flow cytometry (FACS Aria II, BD Biosciences, San Jose, USA).

Results:

Corneal infiltrating NK cells constituted 17.4% of corneal infiltrating lymphocytes and 17.6% of aqueous humor lymphocytes. Cytokine-secreting NK cells in cornea (41.2±9.8) and aqueous humor (40.8±7.73) were significantly more compared healthy blood (11.3±2.0) (p=0.011, p=0.002, respectively). Cytotoxic CD16brCD56dim NK cells were lower in cornea (7.3±3.5) and aqueous humor (19.6±3.1) compared to blood (70.1±2.4) (p=0.001, p=0.002, respectively). However, the CD16brCD56- cytotoxic NK cells were more abundant in cornea (51.5±8.5) and aqueous humor (39.5±5.6) compared to healthy blood (18.4±1.3) (p=0.001, p=0.003, respectively). PD-1 expression was similar among these groups.

Conclusions:

The number of cytokine-secreting and cytotoxic CD16brightCD56- NK cells was significantly higher, while CD16brightCD56dim cytotoxic NK cells was lower in cornea and aqueous humor of corneal rejection patients compared to peripheral blood of healthy subjects. These cells also didn’t show increased PD-1 expression, which we have shown in other corneal infiltrating lymphocytes subsets previously. The active phenotype of these cells might contribute to local inflammatory state by cytokine secretion and tissue damage by antibody dependent cellular cytotoxicity.

Financial Disclosure:

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