Allogeneic corneal tolerance in rodents with long-term graft survival.
BACKGROUND
Healthy C57BL/6 orthotopic corneal allografts in place for more than 8 weeks in BALB/c mice (acceptor8w+) can survive indefinitely due to active suppression of the donor-specific delayed-type hypersensitivity (DTH) response. This suggests a state of tolerance in the acceptor mice, however, the mechanism(s) underlying this acceptance remains to be demonstrated. We investigated the relationship between tolerance-induction and the DTH response using murine re-grafting models to explore the possibility of promoting allogeneic corneal regraft acceptance in high-risk graft beds.


METHODS
Acceptor8w+ BALB/c mice received C57BL/6- or C3H corneal regrafts onto the same eye. Re-grafting models were prepared by inducing corneal neovascularization in the graft beds of naive BALB/c mice 2 weeks before corneal allografting. These mice were intravenously (iv) injected with purified splenic T cells or T-cell-depleted splenocytes from acceptor8w+ mice at the time they received re-grafts of C57BL/6 corneas. We also iv injected acceptor8w+ splenocytes into mice bearing healthy primary corneal allografts for 4 weeks (acceptor4w) and assessed their DTH response to C57BL/6 alloantigen(s). In those experiments, acceptor4w mice received a C57BL/6 corneal regraft onto the same eye.


RESULTS
In all acceptor8w+ mice there was indefinite survival of C57BL/6-, but not of C3H regrafts. The iv injection of T cells, but not of T-cell-depleted populations, from acceptor8w+ splenocytes promoted allograft survival. Acceptor4w mice iv injected with acceptor8w+ splenocytes manifested a reduced C57BL/6-specific DTH response and the survival rate of C57BL/6 regrafts was increased from 0% to 87.5%.


CONCLUSIONS
As donor-specific T cells from acceptor8w+ mice induced prolonged regraft survival, we posit that the active suppression of DTH responses by T cells may have contributed to indefinite allogeneic regraft survival via the induction of corneal allograft tolerance.
Yamada
Jun
J
Department of Ophthalmology, Meiji University of Oriental Medicine, Kyoto, Japan. jyamada@ophth.kpu-m.ac.jp
Hamuro
Junji
J
Sano
Yoichiro
Y
Maruyama
Kazuichi
K
Kinoshita
Shigeru
S
D019264:Adoptive Transfer; D000818:Animals; D016039:Corneal Transplantation / Q000009:adverse effects; D006085:Graft Survival / Q000502:physiology; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012086:Reoperation; D013601:T-Lymphocytes / Q000502:physiology / Q000637:transplantation; D013997:Time Factors; D014019:Tissue Donors; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous