Differential contribution of natural killer cells to corneal graft rejection in 3-week-old versus mature rats.

BACKGROUND

The aim of this study was to compare immunologic graft rejection in adult and 3-week-old immature recipients in the rat keratoplasty model.

METHODS

Forty orthotopic penetrating keratoplasties were performed in four different donor-recipient combinations. Group 1 consisted of adult Fisher donors and adult Lewis recipients, group 2 consisted of adult Fisher donors and immature Lewis recipients, group 3 consisted of adult Lewis donors and recipients, and group 4 consisted of adult Lewis donors and immature Lewis recipients. An immunohistologic evaluation of the grafts was performed on day 14.

RESULTS

Grafts in both allogeneic groups (groups 1 and 2) showed infiltration with CD4+ cells, CD8+ cells, natural killer (NK) cells, interleukin-2-receptor+ cells, macrophages, and intercellular adhesion molecule-1+ cells. The density of infiltrating CD4+, CD8+, interleukin-2-receptor+, and intercellular adhesion molecule-1+ cells in the graft stroma, however, was statistically significantly lower in the immature group (group 2) than in the adult group (group 1). The density of CD161+ NK cells, in contrast, was statistically significantly higher in the immature group than in the adult group. There were no or only a few infiltrating inflammatory cells in grafts of both syngeneic groups (groups 3 and 4).

CONCLUSIONS

We were able to establish for the first time an animal model for keratoplasty in infants that showed that the mechanism of graft rejection in young recipients seems to be different from that in mature rats. In adult recipients, alloreactive T cells are the main mediators of rejection, whereas NK cells seem to play a more dominant role in immature recipients.