Antigen-specific accumulation of naïve, memory and effector CD4 T cells during anterior uveitis monitored by intravital microscopy.

Uveitis is an immune-mediated ocular disease and a leading cause of blindness. We characterized a novel model of uveitis with intravital microscopy. Transfer of ovalbumin-specific T cells from DO11.

A signal through OX40 (CD134) allows anergic, autoreactive T cells to acquire effector cell functions.

To study mechanisms of peripheral self-tolerance, we injected small numbers of naive CD4(+) TCR-transgenic T cells into mice expressing the MHC/peptide ligand under the control of an MHC class II promoter. The donor T cells expand rapidly to very large numbers, acquire memory markers, and go out into tissues, but the animals remain healthy, and the accumulated T cells are profoundly anergic to restimulation with Ag in vitro. Provision of a costimulatory signal by coinjection of an agonist Ab to OX40 (CD134), a TNFR family member expressed on activated CD4 T cells, results in death of the mice within 12 days.

APCs in the anterior uveal tract do not migrate to draining lymph nodes.

The migration of APCs from sites of infection and their maturation are critical elements in the generation of immune responses. However, the paths by which intraocular Ags migrate to draining lymph nodes are not known because the eye has limited lymphatic vessels. To date, only dendritic cells from the cornea and conjunctiva have been shown to emigrate.

Immune mechanisms in uveitis. What can be learned from in vivo imaging?

In many aspects, in vivo imaging is superior to other techniques, such as conventional histology, because it allows the stepwise process of leukocyte migration to be dissected. The potential uses of the in vivo imaging techniques have yet to be achieved. The transfer of lymphocytes with fluorescent dyes can be marked.