Correlation of anterior chamber-associated immune deviation with suppression of corneal epithelial rejection in mice

Abstract

Purpose: The authors investigated the effect of anterior chamber corneal (AC) inoculation of genetically graft-identical antigen on T-cell immunity and the suppression of alloepithelial rejection in mice.

Methods: Antigen-specific suppression of delayed-type hypersensitivity (DTH) and suppression transferability were tested in BALB/c mice injected with irradiated allogeneic B10.D2 splenocytes into AC. Other groups of BALB/c mice received irradiated B10.D2, BALB/c, or C3H/He splenocytes in the AC of the right eye. Seven days later, B10.D2 or C3H/He corneal lenticules were grafted at the limbus of the left eye (keratoepithelioplasty). Alloepithelial rejection of each grafted eye was evaluated according to clinical findings. The DTH response of the keratoepithelioplasty recipients against B10.D2 minor antigen was tested at the end of clinical observation (4 months after grafting). Also examined was spleen component transfer from BALB/c mice with AC inoculation of B10.D2 splenocytes to syngeneic acceptors and its effect on suppression of epithelial rejection against B10.D2 antigen.

Results: Inoculation of B10.D2 splenocytes into BALB/c AC induced antigen-specific DTH suppression, which suppression was transferable. During the 4-month observation period, AC inoculation of B10.D2 minor antigen significantly enhanced the survival of B10.D2-derived epithelium, but not of C3H/He-derived epithelium, in BALB/c mice. However, AC inoculation of BALB/c or C3H/ He splenocytes did not enhance B10.D2 epithelial survival in BALB/c mice. Incapability of antigen-specific DTH response generation was observed in the BALB/c mice with B10.D2 splenocytes in the right AC and B10.D2-derived epithelium in the left eye. Single transfer of spleen components from BALB/c mice with AC inoculation of B10.D2 splenocytes to syngeneic acceptors only delayed B10.D2 minor antigen-stimulated epithelial rejection, whereas supplementary transfers of the identical spleen components at different time intervals showed more significant effect in rejection delay.

Conclusions: The results showed that AC inoculation of B10.D2 splenocytes in BALB/c mice induced antigen-specific suppression of DTH response, in a phenomenon termed anterior chamber-associated immune deviation (ACAID). It also was shown definitely that ACAID can suppress alloepithelial rejection in a murine keratoepithelioplasty model. Adoptive transfer of splenocytes from ACAID-induced mice merely affords short-term suppression of epithelial rejection, suggesting that an additional mechanism may be involved in ACAID maintenance.