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G. Amescua, F. Collings, X. Yang, V.L. Perez; Priming and Recruitment of CD4+ T Cells in High Risk Corneal Allografts . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5868.
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To demonstrate that CD4+ T cell priming and recruitment is essential in the rejection of high risk (HR) corneal allograft.
Orthotopic allogeneic (Balb/c to C57BL/6) were performed in high risk vascularized recipients. Clinical scores were documented and eyes were enucleated at 24 hrs, 72 hrs, 7 days and 14 days for immunohistochemical stains with CD3, CD4 and CD8. Priming of T cells was tested using IFN–gamma ELISPOT assay of lymph nodes cells collected at day 10. To test the role of T cells in graft rejection, high risk recipients were depleted of CD 4 T cells with anti–CD4 antibodies (i.p.) and orthotopic allogeneic grafts were performed in vascularized high risk RAG –/– mice.
The rejection of high risk corneal allografts correlated with the recruitment and infiltration of CD4 T cells from day 7 through day 14. T cell priming was confirmed in the ipsilateral lymph nodes by increased frequency of IFN–gamma producing cells. In contrast to the 100% rejection rate observed in untreated high risk corneal allograft recipients, 25% rejection rate was seen in CD4 depleted high risk mice. Moreover, high risk vascularized Rag –/– recipients had a 100% survival rate.
CD4+ T cells play an essential role in the rejection of high risk corneal allografts. Priming and recruitment occurs at early time points after transplantation and blockade of this process could potentially be targeted to improve the poor survival rate associated with high risk corneal transplantation.
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