Corneas from mice incompatible at both major histocompatibility complex (MH
C) 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 determi
ned in vitro, Over 90% of corneal allografts suffered alloantigen-induced i
nflammatory reaction within the second or third week after surgery, However
, only 56% of grafts in unmodified and 75% of grafts in high-risk recipient
s were irreversibly rejected, Cells obtained from draining lymph nodes from
the vicinity of the eye of the corneal graft recipients produced significa
ntly 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-MH
C or third-party alloantigens, No changes in cytokine production were detec
ted in spleen, The enhancement of IL-10 production in the vicinity of the e
ye was a consequence of corneal grafting and did not correlate with the fat
e of the graft. The results thus show that orthotopic corneal transplantati
on 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 percenta
ge of corneal allografts.