Abstract

An alternative model for corneal allografting termed the reverse corneal allograft reaction (RCAR) was developed in this study. Spleen cells from an alloimmunized donor were injected into the corneal stroma of the immunizing donor strain or were restimulated in mixed lymphocyte culture and then injected into the corneal stroma of the immunizing strain. The reaction began as a circular opaque site that spread and became irregularly shaped during the first 5 days after cell injection. The epithelial surface of the cornea became uneven and epithelial cell erosions were noted. Histological examination revealed that corneal stromal keratocytes at the site of inoculation had undergone degeneration and the injected cells had migrated toward the epithelial-stromal boundary, wherein a disruption of the basement membrane and disintegration of the epithelial cells occurred. Purified spleen cell subsets injected separately did not mediate the reaction. A suspension of T lymphocytes and class II antigen-positive macrophagelike cells was required to cause the RCAR. This reaction, which mimics a delayed-type hypersensitivity response, was transient, reaching a peak by day 5 and waning by day 8. This experimental model of the corneal allograft reaction shows promise for the study of cells and mediators of the corneal allograft reaction and can be employed as a reproducible system in which to test drug therapies for the treatment of corneal allograft rejection.

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