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E Fedoseyeva, TF Ng, N Anosova, BM W Illigens, JW Streilein, G Benichou; De novo Post-transplant Autoimmunty to Retinal Antigens and its Role in Retinal Graft Accommodation . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2290.
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Purpose: We have shown that tissue-specific autoimmunity is an essential element of the rejection of heart transplants. Here, we investigated whether such type of response is triggered in mice after retinal transplantation. Methods: We used a fully mismatched C57BL/6 (H-2b) (B6) - BALB/c (H-2d) (B/C) donor-recipient combination. Mice were transplanted with either adult or neonatal retinal (NNR) sheets into the vitreous cavity (VC, immune-privileged site) and under the kidney capsule (KC, non-immune privileged site). T cell responses to donor MHC antigens (alloresponse) and to interphotoreceptor retinoid-binding protein (IRBP) (autoimmunity) were measured 12 days after transplantation by ELISPOT. IRBP represents a target autoantigen in T cell-mediated inflammatory eye autoimmune disease, experimental autoimmune uveitis (EAU). Retinal graft deterioration was evaluated histologically. Results: Adult retinal allografts placed into VC induced potent IRBP-specific T cell responses. No IRBP-specific responses were detected in mice transplanted with syngeneic adult retinas. Placement of B/C graft into B6 mice (moderately susceptible to EAU) triggered potent Th1 type T cell reactivity to IRBP whereas B/C recipients (resistant to EAU) developed Th2 type of anti-IRBP autoimmunity after B6 retinal graft transplantation. Th2 type of retinal-specific post-transplant autoimmunity appeared to be less pathogenic in that retinal grafts enjoyed better survival in Th2-prone BALB/c hosts. No response to IRBP was observed after transplantation of NNR into VC. However, both syngeneic and allogeneic NNR grafts induced potent autoimmunity when placed in a non-immune-privileged site (KC). Interestingly, degeneration of syngeneic transplants placed under the KC correlated with the strength of IRBP-specific responses. Conclusions: Tissue-specific response to IRBP is induced after transplantation of adult retina into VC and requires initial alloresponse for its initiation. EAU susceptibility influences host&lsquo;s anti-graft immune response and graft survival after retinal transplantation. Neonatal retinal grafts are not immunogenic in the VC. However, in a non-immune-privileged site (KC), retinal antigens are potent immunogens and can contribute to the destruction of retinal grafts in the absence of alloresponse.
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