Interactions between lymphocytes and cells of the blood-retina barrier: mechanisms of T lymphocyte adhesion to human retinal capillary endothelial cells and retinal pigment epithelial cells in vitro.

We have studied the adhesion of human CD4+ lymphocytes to cultured human retinal vascular endothelial cells (EC) and human retinal pigment epithelial cells (RPE), both of which comprise the cellular components of the blood-retina barrier. We have observed differences in the lymphocyte-RPE and the lymphocyte-EC interactions. Firstly, RPE cells were found to express high levels of the adhesion molecule ICAM-1 constitutively, whereas EC expressed ICAM-1 only after induction with IFN-gamma. In addition, lymphocyte binding to normal and minimally stimulated RPE (5 U/ml, 4 hr) was predominantly ICAM-1 dependent, but after maximal stimulation (500 U/ml, 4 days), increased lymphocyte adhesiveness included an ICAM-1-independent component, which was apparently not due to involvement of MHC class II or CD2 molecules. In contrast, binding of lymphocytes to unstimulated EC involved both an ICAM-1-dependent and an ICAM-1-independent mechanism, the latter being subject to inhibition by monoclonal antibody to CD2. Studies of adhesion at 4 indicated that no binding occurred to normal or stimulated RPE, but binding to EC was observed, albeit reduced to 50% of the 37 binding level, and this implies that the LFA-3/CD2 adhesion pathway may also be involved in lymphocyte binding to EC. Overall, the results indicate a functional difference between RPE and EC affecting T-cell adhesion, migration and activation at the blood-retinal barrier, which must be considered when devising therapies to prevent lymphocyte infiltration of the eye.