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H. Taniguchi, Y. Kitahara, M. Oshima, H. Akiba, H. Yagita, M. Azuma, J. Hori; Role of B7-H3/TLT-2 Pathway on Corneal Allograft Survival. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1550.
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We have reported that B7-H3, a costimulatory signal B7 family molecule, is an essential molecule for acceptance of corneal allografts and induction of anterior chamber-associated immune deviation (ACAID). Recently, Triggering receptor expressed on myeloid cells-like transcript-2 (TLT-2) has been identified as a B7-H3 receptor. This study analyzed the intraocular expression of B7-H3. In addition, we analyzed the inhibition and molecular function of the B7-H3/TLT-2 pathway using 3 different antibodies in a corneal transplant model.
Expression of B7-H3 was assessed by RT-PCR in the cornea, iris-ciliary body, and retina of normal mouse eyes. Normal corneas of C57BL/6 were transplanted orthotopically into normal eyes of BALB/c mice. Anti-B7-H3 monoclonal antibody (mAb) (MJ18) (which does not inhibit binding to TLT-2), anti-B7-H3 mAb (M1H35) (which does inhibit binding to TLT-2), anti-TLT-2 mAb (M1H49), or control rat IgG were administered intraperitoneally, and allograft acceptance was analyzed.
B7-H3 was constitutively expressed in the cornea, iris-ciliary body, and retina of normal eyes. In groups treated with anti-B7-H3 mAbs or anti-TLT-2 mAb, all allografts were rejected. Compared to the control group, survival was significantly shortened (p<0.05). Compared to anti-B7-H3 mAb (MJ18) that did not inhibit binding to TLT-2, anti-B7-H3 mAb (M1H35) that did inhibit binding to TLT-2 significantly shortened survival.
B7-H3 is constitutively expressed in ocular tissue. B7-H3/TLT-2 pathway plays a suppressive role in immune response of the corneal allografts. B7-H3 expressed in the ocular tissue may facilitate allograft survival.
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