Graft survival and cytokine production profile after limbal transplantation in the experimental mouse model

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Abstract

Purpose To evaluate the immune response in the experimental model of orthotopic limbal allo- and xenotransplantation in the mouse.

Methods Allogeneic (C57BL/6 to BALB/c mouse), xenogeneic (Lewis rat to BALB/c mouse) and syngeneic (BALB/c to BALB/c mouse) limbal transplantations were performed. The rejection of limbal graft was scored according to the corneal opacity. The expression of IL-2, IFN-gamma, IL-4, IL-10 and inducible nitric oxide synthase (iNOS) were detected by Real-time PCR in the graft. The donor cell survival was determined by Real-time PCR after transplantation. The recipients were treated with systemic monoclonal antibodies (mAb) anti-CD4 and anti-CD8 and with saline in the control group.

Results The allografts were rejected in 9.0 ± 1.8 days and xenografts in 6.5 ± 1.1 days after transplantation, syngeneic limbal grafts survived permanently. Distinct pattern of Th1 and Th2 cytokine production and intragraft expression of the iNOS gene were detected during rejection. Limbal grafts were promptly rejected by Th1 (allogeneic group) or by Th2 (xenogeneic group) type of immune response involving CD4+ cells and iNOS expression. The mean survival time of allogeneic and xenogeneic grafts was prolonged by systemic treatment of mAb anti-CD4. Treatment with mAb anti-CD8 did not extend the graft survival.

Conclusion The experimental model of limbal transplantation is useful for testing various immunosuppressive approaches to treat rejection after transplantation. The anti-CD4 mAb treatment presents promising immunosuppressive treatment after limbal transplantation.

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