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C. H. Lau, C. Watte, J. Stein-Streilein; In vivo Anti-ly49c/i Treatment Prevents the Development of Acaid and Allogeneic Corneal Graft Survival. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3629.
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The purpose of this study was to analyze the role of the Ly49 C/I inhibitory receptor in the development of long term corneal graft survival.Background: When C57Bl/6 (B6) corneas are transplanted to BALB/c hosts, 50% of the corneal grafts survive indefinitely. Graft survival is related to the development of Anterior Chamber Associated Immune Deviation (ACAID) since mice that lack iNKT cells do not develop ACAID, reject 100% of the grafts. Previously we reported that ACAID is dependent on a subpopulation of invariant (i)NKT cells that express the inhibitory Ly49 C/I molecule since blocking this molecule in vivo or in vitro with Mab 5E6 or Mab 5E6 (Fab’)2 fragments prevented the development of ACAID and the production of NKT cell-derived IL-10.
To test if the Ly49 C/I molecule on the NKT cell plays a role in the corneal graft survival, we compared the survival rate of B6 corneal grafts transplanted into BALB/C mice that were pre-treated or not with anti-Ly49C/I mAb (clone 5E6). Female C57BL/6 mice (8-12 weeks old) were used as corneal allograft donors. BALB/c (8-12 weeks old) recipient mice were inoculated (i.p.) with mAb 5E6 (100ug in 100ul PBS per mouse) or PBS only one day prior to grafting. Eyelid and corneal sutures were removed 3 and 7days post-operatively, respectively. Grafts were assessed weekly up to 8 weeks and graft acceptance equivalent to an corneal opacity score ≤1.
As previously reported, 100% of syngeneic grafts were accepted, compared to 40% of allografts accepted (n=10 per group). When mice were pretreated with mAb to anti-Ly49 C/I no grafts survived. Mice that received vehicle only showed 50% survival of their allografts (n=10 per group). In other studies ACAID-mediated DTH suppression did not develop when mice were pretreated with anti-Ly49C/I mAb or F(ab’)2 fragments showing that blocking the molecule and not removal of the Ly49C/I+ NKT cell population, prevented the development of ACAID.
In vivo treatment of recipient BALB/c mice with anti-Ly49 C/I mAb interferes with the prolonged survival of B6 corneal allografts. These data support a novel role for the family of Ly49 inhibitory molecules in corneal graft survival. The requirement of Ly49 C/I ligation for the development of ACAID contributes to graft acceptance. This work was supported in part by NIH grants: EY11983, EY016476.
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