ABSTRACT
The limbus, the area between the vascularized conjunctiva and avascular cornea, has a significant resident population of MHC class II+ LC that when stimulated
can be recruited into the cornea (11,18-21). Our laboratory has identified interleukin-1 (IL-1), a potent pro-inflammatory cytokine, as playing a major role in the recruitment of limbal APCs into the cornea. We have shown that the early expression of IL-1 by the inflamed cornea leads to profound upregulation (even within hours) in the expression of the cell adhesion molecule ICAM-1 by the limbal vascular endothelium, which precedes the recruitment of leukocytes to the peripheral cornea (22). The role of IL-1 is confirmed in the transplant model in which the recruitment of host-derived LCs into the allografts is suppressed as a result of IL-1 blockade (23). However, IL-1 is not the sole cytokine involved in this process. Tumor necrosis factor-alpha (TNF-α) also plays an important role. Indeed, local suppression of TNF-α signaling can significantly suppress limbal LC recruitment into the cornea by effective suppression of gene transcription for RANTES and MIP-1β (24), two principal ligands of CCR5, a chemokine receptor that mediates LC recruitment into the cornea (25).
