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J. Yamada, K. Maruyama, Y. Sano, J. Hamuro, S. Kinoshita; Role of Donor MHC Molecule in Corneal Graft Rejection . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3210.
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Purpose: We previously noted that recipients bearing long-standing healthy corneal allografts (acceptors) permanently accepted secondary-graft corneas (re-grafts) from the same donors. Since minor histocompatibility (H) antigens, rather than major histocompatibility complex (MHC) antigens, pose the greater barrier to graft acceptance in orthotopic corneal graft, we examined the graft survival onto long-term acceptors of third party corneal re-grafts whose minor H antigens are matched with first donor strain. Methods: BALB/c (H-2d) recipients bearing C57BL/10 (H-2b) or B10.D2 (H-2d) healthy corneal allografts for more than 12 weeks were prepared. The two groups received either B10.D2 or C57BL/10 corneal re-grafts onto the same eye. (B10.D2 mice share the same minor H antigens as C57BL/10 mice) Corneal rejection was evaluated by slitlamp microscopy. After the observation periods, splenocytes of recipients were cultured with irradiated B10.D2 splenocytes to evaluate minor H antigen-specific proliferation. Results: When BALB/c acceptors received corneal re-grafts from the same strain as the first donor grafts, all C57BL/10 (n = 10) or B10.D2 (n = 10) corneal re-grafts were accepted indefinitely. In contrast, all BALB/c recipients accepting B10.D2 first allografts rejected C57BL/10 re-grafts within 3 weeks (n = 5). Secondly, all BALB/c recipients accepting C57BL/10 first allografts rejected B10.D2 re-grafts within 3 weeks (n = 8). The proliferative extent of either C57BL/10 rejector or B10.D2 rejector splenocytes was significantly greater than that of C57BL/10 acceptor and B10.D2 acceptor mice. Conclusions: MHC + minor H disparate corneal re-grafts did not enhance graft survival even in the presence of minor H antigen-specific tolerance. This high frequency of graft rejection indicates that minor H antigen specific tolerance was abrogated through induction of inflammatory milieu, probably due to high-risk graft beds. Second, minor H only incompatible corneal re-grafts did not survive even in the presence of MHC + minor H antigen-specific tolerance. This paradox indicates that moderately primed memory cell to minor H antigen in the first allograft might be boosted at the stage of second allograft in connection with compatible MHC molecules, resulting in efficient antigen presentation. MHC molecules in donor graft, regardless of low MHC expression, may display the critical role in allograft rejection.
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