NK cell depletion delays corneal allograft rejection in baby rats

PURPOSE: Penetrating keratoplasty has a very poor outcome compared with adults if performed in the first years of life. Rejection in these young patients occurs even in the absence of known immunological risk factors. Recently, a baby rat model was introduced and an essential contribution of natural killer (NK) cells during allograft rejection was suggested. To analyze this, NK cells were depleted in baby rats before keratoplasty. METHODS: Allogeneic keratoplasty was performed between Lewis and Fisher rats. The recipient's ages were 10 and 3 weeks, respectively. NK cells were depleted by an intraperitoneal injection of a monoclonal antibody. All experiments were controlled by the injection of isotypic control antibodies and syngeneically. Survival rates were calculated and cellular infiltrates were analyzed histologically. RESULTS: NK cell depletion did delay median graft survival times in a statistically significantly way compared with the control animals (p<0.01). At median rejection time points, macrophages, CD4(+) T cells and CD25(+) leukocytes infiltrated to a greater extent in the depleted recipients. No significant changes in the cell numbers of infiltrating CD8(+) T cells were observed. CONCLUSIONS: We conclude that NK cells play a role during allograft rejection in baby rats, but their effect is replaceable. A greater infiltration of macrophages and CD4(+) T cells suggests that they might compensate for the missing NK cells’ response in this experimental setting. Our results represent another step toward understanding the complex mechanisms of an accelerated corneal graft rejection in infant recipients.