Fc gamma Receptors & Herpes Stromal Keratitis

描述(申请人提供)：我们实验室以前的研究已经证明，在HSV-1角膜感染后，被动地将小剂量的单抗转移到病毒糖蛋白可以防止永久性失明的角膜炎症的建立。抗体如何发挥其保护作用尚不清楚。然而，由于病毒中和F(Ab)2时没有看到保护作用，因此用片段代替完整的抗体Fcγ受体(FcGammaRs)被认为是参与的。最近的进展导致了对FcGammaRs的意义的根本修改。现在人们认识到两种类型--一种是当连接时激活细胞，另一种是抑制细胞激活。当这两种类型由同一细胞表达时，共连接引发的净细胞反应被认为取决于两种相反信号的表达比率。我们将使用野生型和FcgR基因敲除小鼠来检验这样的前提，即通过共连接的病毒抗原：抗体复合体有利于FcgR负信号，从而抑制疱疹间质角膜炎的发展。我们的研究将为FcGammaRs在眼组织中的表达和功能提供新的信息，并可能导致控制角膜炎症的新策略。

DESCRIPTION (provided by applicant): Prior studies in our laboratory have demonstrated that passive transfer of low dose monoclonal antibody to viral glycoproteins given after HSV-1 corneal infection can prevent the establishment of permanent blinding corneal inflammation. How antibody exerts its protective effect is not known. However, since no protection was seen when virus neutralizing F(ab)2, fragments were given in place of intact antibody Fc gamma receptors (FcgammaRs) were though to be involved. Recent advances have led to a fundamental revision of the significance of FcgammaRs. Two types are now recognized - those that when ligated activate cells and those which inhibit cell activation. Where both types are expressed by the same cell the net cellular response triggered by co-ligation is thought to depend on the ratio of expression of the two opposing signals. We will use wildtype and FcgR gene knockout mice to test the premise that viral antigen:antibody complexes via co-ligation favor negative FcgR signaling, and so suppress herpes stromal keratitis development. Our studies will provide new information on the expression and function of FcgammaRs in ocular tissue and may lead to novel strategies for controlling corneal inflammation.