Immunologic privilege evoked by histoincompatible intracameral retinal transplants.
In order to examine the fate of intraocular retinal transplants, we placed histoincompatible neural retinas from neonatal BALB/c mice into the anterior chamber (AC) or subconjunctival space of eyes of adult C57BL/6 mice. Clinical and histologic examinations revealed that grafts of developing neural retinal tissue placed within the AC acquired a blood supply, and differentiated into histologically recognizable retinal structures; there was no evidence of inflammation or rejection. By contrast, developing neural retinal allografts placed in the subconjunctival space failed to thrive, and were promptly rejected within 8 days. To examine the nature of the systemic immune response of mice bearing intracameral retinal allografts, C57BL/6 mice, bearing neural retinal allografts from BALB/c donors in their AC for 12 days, were tested for delayed hypersensitivity. When ear challenged with (C57BL/6 x BALB/c)F1 spleen cells, these mice failed to mount significant ear swelling responses, whereas a positive control group of C57BL/6 mice that received neonatal BALB/c retinas implanted in the subconjunctival space displayed vigorous BALB/c-specific delayed hypersensitivity. It is pertinent that, shortly after ear challenge with (C57BL/6 x BALB/c)F1 cells, the previously healthy AC retinal allografts underwent regression and degeneration. Finally, we showed that the spleens of C57BL/6 mice bearing healthy intraocular developing retinal allografts contained suppressor lymphocytes that were revealed in adoptive transfer assays. We conclude that immune privilege is extended to histoincompatible developing retinal transplants placed in the AC of the eye, and that these allografts induce a deviant systemic immune response characterized by impaired expression of delayed hypersensitivity and generation of splenic suppressor cells. We infer that the success of these transplants, compared to similar grafts which are rejected in the subconjunctival space, is predicated upon, and mediated by, the induction of active specific suppression of cell-mediated immunity.
Jiang
L Q
LQ
Department of Microbiology and Immunology, University of Miami, School of Medicine, FL 33101.
Streilein
J W
JW
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D003228:Conjunctiva / Q000473:pathology / Q000637:transplantation; D006085:Graft Survival / Q000276:immunology*; D006648:Histocompatibility; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology*; D007165:Immunosuppression Therapy; D016219:Immunotherapy, Adoptive; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012160:Retina / Q000473:pathology / Q000637:transplantation*; D014184:Transplantation, Homologous / Q000276:immunology