Enhanced IL-10 and decreased IL-2 production after orthotopic corneal transplantation in mice.

: Corneas from mice incompatible at both major histocompatibility complex (MHC) and non-MHC antigens were grafted orthotopically to unmodified and high-risk recipients. Production of interleukin-2 (IL-2) and IL-10 by cells from spleens and draining lymph nodes from corneal graft recipients was determined in vitro. Over 90% of corneal allografts suffered alloantigen-induced inflammatory reaction within the second or third week after surgery. However, only 56 % of grafts in unmodified and 75 % of grafts in high-risk recipients were irreversibly rejected. Cells obtained from draining lymph nodes from the vicinity of the eye of the corneal graft recipients produced significantly elevated amounts of IL-10 and decreased amounts of IL-2. This shift to the Th2 type cytokine response was observed after stimulation of the cells with graft donor MHC antigens, but not after stimulation with donor non-MHC or third-party alloantigens. No changes in cytokine production were detected in spleen. The enhancement of IL-10 production in the vicinity of the eye was a consequence of corneal grafting and did not correlate with the fate of the graft. The results thus show that orthotopic corneal transplantation induces a local shift to the Th2 type cytokine response, which might be considered another factor that contributes to the unique characteristics of the immunity in the eye and to the tolerance of an unusually high percentage of corneal allografts.