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J. Jeong, M. Kim, J. Ko, H. Lee, M. Shin, J. Lee, W. Wee, S.-Y. Seong, H.-J. Moon, S. Akira; The Effect of TLR4 on the Survival of MHC Mismatched Corneal Allograft. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5137. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the role of TLR4 on the MHC mismatched allograft rejection in corneal transplantation
Twenty C57BL/6 wild-type mice and Twelve C57BL/6 TLR4 knock-out(KO) mice were divided into 3 groups for corneal transplantation. Corneal grafts from C3H/HeN mice were transplanted to B6 mice(n=10) or to TLR4-KO mice(n=12). Autografts were transplanted from B6 to B6 mice(n=10). Survival was analyzed based on total graft edema(n=23), and the mice were sacrificed after full rejection. Nine mice were sacrificed in three groups(each n=3) at postoperative 10 days and cervical lymph nodes were collected. CD11c, CD80, CD86, CD4, CD44, CD69, CD25, and FoxP3 were evaluated using flow cytometer(Becton & Dickinson, USA).
Median survival time(MST) of corneal grafts from C3H mice to TLR4-KO were shortened than MST of the others. At 10days, the expression of CD11c and CD80/86 were 2.2% and 27.7% in autograft, 1.88% and 17% in allograft of wild type, and 2.38% and 43.3% in allograft of TLR4 KO. The expression of CD44/CD69 increased to 8.1% in TLR4 KO recipients compared with those of autograft(3.69%) or allograft(5.53%) in B6. The expression of CD25/Foxp3 doubled in TLR4 KO mice compared with those of the other groups. The expression of CD80/86 and CD44/69 were still higher in TLR4 KO mice than in the other groups after full rejection.
TLR4 may have an immune modulatory role on maturation of dendritic cells in ocular surfaces which have gram positive commensals, affecting the survival of MHC mismatched allograft.
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