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Victor L. Perez, Yaohong Tan, Stephanie Duffort, Fernando Cruz-Guilloty, Xiao Mei, Midhat Abdulreda; Male Minor Antigen-Mediated Corneal Graft Rejection. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3143.
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Corneal allograft rejection is T cell-mediated.We have reported previously on T-cell dynamics and movement patterns during corneal graft rejection in major histocompatibility complex (MHC) mismatched transplants. But minor antigen mediated corneal graft rejection is still uncertain. In this work we utilized Marylin CD4 T cell receptor (TCR) transgenic mice to study the graft survival and T cell dynamics during male antigen-mediated corneal graft rejection.
Corneal transplantations were performed with female TCR transgenic Marylin RAG2 knockout (KO) mice (C57BL/6 H-2b). In these mice all the T cells are CD4+ T cells with TCR specific to male Y antigen. Donor corneas were from female and male wt C56BL/6 and wt BALB/c mice. Corneal graft survival was evaluated with a clinical score system. To visualize T cells during graft rejection, Mar mice were backcrossed with EGFP C57BL/6. EGFP+TCR+ CD4+ T cells were purified and injected into RAG KO C57BL/6 mice. 48 hours later corneal transplantation was performed in these reconstituted mice. T cell dynamic and movement were imaged with longitudinal non-invasive fluorescence confocal microscopy. Z-stack images
In Marilyn mice 100% of male BALB/c and male C57BL/6 grafts were rejected from POD14-POD28. There was no difference of the tempo of rejection between male BALB/c grafts and male C57BL/6 grafts (P>0.05). The tempo of rejection was also similar as major MHC mismatched corneal graft rejection (P>0.05). In contrast, all the female BALB/c grafts and female C57BL/6 grafts survived until the end of this experiment. EGFP+ cells were observed with confocal microscopy at post operative day (POD) 1 and subsequently increased in numbers with time. The images and dynamic analysis between major versus minor antigens will be compared with Velocity software.
T cells with TCR specific to male antigen do reject male grafts. This minor antigen-mediated rejection has similar tempo as major MHC mismatched corneal graft rejection, suggesting that efficient T cell activation, regardless of antigen specificity, is required for corneal graft rejection.
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