IMMUNE RESPONSES TO OCULAR ANTIGENS

National Eye Institute

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Abstract

Targeted at learning about inflammatory eye diseases, this project focused in FY 2000 on pathogenic mechanisms of immune-mediated ocular inflammation and cellular processes that regulate immunity against ocular antigens. Noteworthy results include the following: 1.A new experimental system was developed in order to learn about the involvement of different subsets of CD4 T-helper (Th) cells in ocular inflammation. This system determines the capacity of purified populations of Th1 and Th2 cells sensitized against hen egg lysozyme (HEL) to induce inflammation in eyes of mice in which HEL is transgenically expressed in the lens. Purified Th1 lymphocytes were highly pathogenic, producing ocular inflammation at numbers as low as 120,000. In contrast, Th2 cells failed to produce disease even at 30 million per recipient. Th2 cells did induce inflammation, however, when injected into recipients that were irradiated with a sub-lethal dose of 450 Rad. Adding Th2 cells had no effect on disease induced by Th1 in unirradiated mice, but enhanced the inflammation in irradiated recipients. These data indicate that the notion about Th2 cells being "protective" against immune-mediated inflammation is not necessarily correct. 2.The process of tolerance against self ocular antigens was further examined by using Tg mice that express HEL under the control of the alphaA-crystallin promoter ("HEL-Tg" mice). These mice are tolerant by their T-cell compartment against HEL. In addition, HEL-Tg mice fail to develop humoral immune response when immunized with HEL, but our new data show that the B-cell compartment is not tolerized against HEL and can produce antibody when provided with T-cell help. Thus, adoptive transfer of as few as 40,000 HEL-specific Th cells enabled production of substantial levels of HEL antibody in the HEL-Tg mice. Our results provide an experimental model for the process that facilitates production of pathogenic anti crystallin antibody in patients with lens-associated uveitis ("phacoanaphylactic endophthalmitis").