Immunologic phenotype of hosts orally immunized with corneal alloantigens.

PURPOSE

To evaluate the immunologic phenotype of hosts tolerized by oral administration of corneal alloantigens.

METHODS

CB6F1 mice were tolerized by oral administration of allogeneic C3H/Hej corneal epithelial and endothelial cells before receiving heterotopic C3H/Hej corneal allografts. C3H-specific cytotoxic T-lymphocyte (CTL), delayed-type hypersensitivity (DTH), and mixed-lymphocyte responses were evaluated in orally tolerized and control mice. Cytokine profiles of Peyer's patch cells from orally tolerized mice were determined by enzyme-linked immunosorbent assay and mink lung cell culture bioassay.

RESULTS

Oral administration of corneal cells produced a profound inhibition of allospecific CTL, DTH, and mixed-lymphocyte responses. Conjugation with the B subunit of cholera toxin markedly increased the tolerizing activity of corneal endothelial cells, so that a single dose of cholera toxin-conjugated corneal cells inhibited alloimmune responses to the same degree as 10 doses of corneal cells unconjugated with cholera toxin. Peyer's patch cells from orally tolerized mice produced reduced quantities of interferon-gamma and interleukin-2 but produced increased amounts of transforming growth factor-beta and interleukin-10 compared with concentrations in normal control animals.

CONCLUSIONS

Oral administration of cholera toxin-conjugated corneal cells produces a dose-dependent inhibition of allospecific CTL, DTH, and mixed-lymphocyte responses. Orally induced inhibition of cell-mediated immune responses to corneal alloantigens is correlated with a sharp increase in the secretion of transforming growth factor-beta and interleukin-10 and a concomitant suppression of interleukin-2 and interferon-gamma. The well-recognized immunosuppressive characteristics of transforming growth factor-beta and interleukin-10 are suggestive that orally induced tolerance to corneal alloantigens is mediated by these cytokines.