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Victor L. Perez, Yaohong Tan, Stephanie Duffort, Chen Zhibin, Midhat Abdulreda; Dual Role Of Allospecific CD4 And CD8 T Cell Recruitment In Corneal Allograft Rejection. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1148.
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The role of T cells in corneal allograft rejection is well established. However, how CD4 and CD8 T Cell recruitment into the graft causes graft rejection is not understood. In this work we utilized a novel in vivo model to track corneal antigen specific T cells to study this interaction.
Corneal allografts were performed utilizing mice over-expressing ovalbumin in the cornea under the beta-actin promoter as donor, into C57BL6 mice recipient adoptively transferred with green-fluorescently labeled CD8 ova specific OTI T cells and red-fluorescently labeled CD4 ova specific OTII T cells. Graft survival was clinically assessed and recruitment of antigen specific T cells was monitored in vivo using real time in vivo microscopy.
Adoptively transferred C57BL6 mice with OTI and OTII ova specific T cells rejected efficiently OVATg corneal allografts and did not rejected wild type C57BL6 corneal graft isogeneic controls. Rejection correlated with an increased recruitment of both CD4 and CD8 T cells into the graft, however, if CD4 T cells were not present, graft rejection was delayed . In vivo microscopy demonstrate that both cells interact within the corneal graft to induce rejection. Kinetic analysis of effector T cells in the graft show that allospecific CD8 and CD4 T cells move fast in the graft with a high index of velocity and length.
Corneal allograft rejection is dependent on the efficient recruitment of both CD4 and CD8 T cells, however, CD4 T cells are critical in this process. Our novel in vivo model of tracking corneal antigen specific T cells is a useful tool to study mechanisms of corneal allograft rejection
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