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Jun Yamada, Takahiko Hayashi, Junji Hamuro, Satoshi Yamagami, Shigeru Kinoshita; The Role Of Allo-antigen Presentation In Mice Penetrating Keratoplasty Controlled By Mhc Matching. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2377.
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Reportedly, chimeric allografts enjoy graft survival, consisting of BALB/c or C3H/He corneal epithelium (Ep) over a B6 epithelial-denuded corneal stroma/endothelium (S/E), orthotopically placed on BALB/c hosts. Thus, corneal graft Ep, but not S/E, is believed to play a role in allosensitization in mice penetrating keratoplasty. Since the minorH alloantigens are the main target for allograft rejection, we examined the graft survival of MHC-matched chimeric allografts and investigated the minorH-specific allosensitization.
Chimeric allografts consisting of B6 (H-2b), B10.D2 (H-2d), and BALB/c (H-2d) corneas were placed on BALB/c hosts. Immunized controls were prepared by subcutaneous insertion of central 2-mm diameter allogeneic Ep or S/E. Graft survivals and minorH alloantigen-specific delayed-type hypersensitivity response were evaluated.
BALB/c mice inserted with either B6-Ep, B10.D2-Ep, B6-S/E, or B10.D2-S/E corneas subcutaneously for 2 weeks displayed positive DTH (n=5 each). B6-Ep+BALB/c-S/E, but not B10.D2-Ep+BALB/c-S/E, grafted BALB/c mice displayed positive DTH at 4 weeks postoperative (n=10 each, 100% survival). Though BALB/c-Ep+B6-S/E allografts enjoyed graft survival (n=10, 90% survival), only 33% of BALB/c-Ep+B10.D2-S/E allografts survived indefinitely (n=15). BALB/c-Ep+B6-S/E grafted mice with healthy corneas displayed negative DTH response (n=7) at 4 weeks postoperative. In contrast, BALB/c-Ep+B10.D2-S/E grafted mice with healthy corneas displayed positive DTH response at 4 weeks postoperative (n=5). After ear challenge by B10.D2 splenocyte, all BALB/c-Ep+B6-S/E and BALB/c-Ep+B10.D2-S/E allografts were rejected. B10.D2-Ep+B6-S/E chimeric allografts survived indefinitely (n=10, 100% survival).
Under orthotopical corneal allografts, MHC-mismatched corneal Ep possesses the capacity for sensitizing the host, but MHC-matched corneal Ep does not. In contrast, MHC-mismatched corneal S/E does not possess the capacity for sensitizing the host, but MHC-matched corneal S/E does. Donor-derived stromal CD11b-positive macrophages may present alloantigen under MHC-matched stromal allografts. Thus, it may be necessary to regulate stromal-layer allogeneic-antigen-presenting cells in MHC-matched allograft cases. In addition, the mechanism of the rejection in DSEAK can be explained.
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