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Hiroko Taniguchi, Hidenori Hase, Hisaya Akiba, Hideo Yagita, Miyuki Azuma, Junko Hori; Role of B7-H3/TLT-2 pathway in immune privilege of corneal allografts. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5734.
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B7-H3 belongs to the B7 superfamily, a group of molecules that co-stimulate or down-modulate T-cell responses. Recently, triggering receptor expressed on myeloid cells-like transcript-2 (TLT-2) has been identified as a B7-H3 receptor. We have previously reported that B7-H3 is constitutively expressed in ocular tissue and B7-H3/TLT-2 pathway is necessary for corneal allograft survival. To further investigate the mechanisms B7-H3-associated immune suppression, we examined anterior chamber associated immune deviation (ACAID) in vivo and destruction of corneal endothelial cells (CECs) by allo-reactive CD4+ T cells in vitro.
Allo-antigen-specific ACAID model was used. BALB/c mice received anterior chamber (AC) injection of C57BL/6 (B6) splenocytes 2 weeks prior to subcutaneous (SC) immunization. Induction of allo-specific ACAID was assessed by ear challenge with B6 splenocytes at 1 week after immunization. Recipients were administrated intraperitoneally with 0.2 mg of anti-B7-H3 mAb, anti-TLT-2 mAb, or control rat IgG, three times a week for 3 weeks after AC injection. As a different set of experiments, B6 cornea pre-treated with anti-B7-H3 mAb or control rat IgG were incubated with CD4+ T cells for 6 h. CD4+ T cells were purified from the spleen of BALB/c that were presensitized by SC immunization with B6 splenocytes or with third-party (C3H/He) splenocytes, or from the spleen of naive BALB/c, B6 or C3H/He mice. Dead CECs stained with propidium iodide were counted and compared.
ACAID was abolished in the recipients treated with either anti-TLT-2 or anti-B7-H3 mAb. The number of dead CECs was significantly larger in anti-B7-H3 mAb-treated corneas than in control IgG-treated corneas after incubation with alloreactive CD4+T cells. The number of dead CECs was also significantly larger in anti-B7-H3 mAb-treated corneas than in control corneas after incubation with CD4+T cells activated against third-party allo-antigens.
B7-H3/TLT-2 pathway is involved in the induction of ACAID. B7-H3 expressed on CECs plays a role in protecting CECs from destruction by activated CD4+ T cells. Thus, B7-H3/TLT-2 pathway maintains acceptance of corneal allografts by inducing ACAID as a systemic effect and suppressing allo-reactive CD4+ T cells within the eye as a local effect.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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