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V.L. Perez, G. Amescua, T. El–Sawy, X. Yang, F. Collings; Early Inflammation After Corneal Transplantation in High Risk Vascularized Corneas Enhances T Cell Recruitment and Graft Rejection . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1783.
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© ARVO (1962-2015); The Authors (2016-present)
The outcome of corneal allografts in vascularized "high risk" recipients is dismal. We hypothesize that independent of early T cell priming, the increased early innate inflammatory microenvironment in high risk corneal recipients enhances T cell recruitment and is responsible for the increased rate of graft rejection.
To study the effects of early innate inflammatory responses, orthotopic allogeneic corneal grafts were performed in non high risk and high risk vascularized Rag –/– recipients that lack T and B cells (Balb/c to Rag –/– C57BL/6). Twenty–two days after corneal grafting 1x106 purified T cells from EGFP transgenic mice were adoptively transferred by IV tail injection. Graft survival was documented and recruitment of EGFP positive T cells was monitored at different time points by in vivo fluorescent stereomicroscopy.
Corneal allografts performed in non high risk and high risk Rag –/– recipients survived indefinitely. Accepted allografts in non high risk Rag –/– that received T cells continue to survive up to twenty days after adoptive transfer. A transient accumulation of EGFP positive T cells was observed in the host bed and graft, but resolved by day 10. In contrast, accepted allografts in high risk Rag –/– succumbed to rejection 7 days after the adoptive transfer of T cells. Corneal allograft rejection correlated with the increased recruitment and accumulation of EGFP positive T cells in the graft.
The presence of T cells immediately after transplantation is required for the rejection of non high risk and high risk orthotopic corneal allografts. However, in the absence of T cells only high risk corneal allografts are "immunologicaly marked" and can be later recognized by allo–antigeneic T cells. These results confirm our hypothesis that early innate inflammatory signals regulate adaptive T cell responses and can be an important mechanism that explains the dismal outcome in high risk corneal graft recipients.
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