Draining Lymph Nodes of Corneal Transplant Hosts Exhibit Evidence for Donor Major Histocompatibility Complex (MHC) Class II–positive Dendritic Cells Derived from MHC Class II–negative Grafts

TLDR

The study aimed to test whether corneal grafts contain passenger leukocytes that can migrate to draining lymph nodes by tracking GFP‑labeled donor cells in allogeneic recipients. GFP‑labeled donor cells were tracked in the draining cervical lymph nodes of allogeneic recipients, with enhanced migration observed in inflamed beds. Donor GFP+ cells, including normally MHC class II–negative CD11c+ dendritic cells that upregulate class II after transplantation, migrated to cervical lymph nodes, displayed allostimulatory capacity (albeit weaker than splenic controls), and these findings challenge the view that the cornea is immune privileged because of absent resident lymphoreticular cells.

Abstract

To examine the widely accepted dogmas that corneal grafts lack passenger leukocytes or cells capable of migrating directly to lymph nodes (LNs), we tracked the migration of corneal graft-derived transgenic green fluorescent protein (GFP; Iab) cells into the draining LNs of allogeneic (Iad) recipients. GFP+ cells were identified in cervical LNs several hours after transplantation, and this traffic was significantly enhanced when grafts were placed in inflamed recipient beds. Draining cells were Iab+, CD45+, and CD11c+, and examination of ungrafted corneas revealed numerous similarly CD45+CD11c+CD3−CD8α− cells that uniformly lacked major histocompatibility complex (MHC) class II expression; transmission electron microscopy confirmed the presence of morphologically similar cells. After transplantation, or placement in culture, these CD11c+ cells became class II+ in a time-dependent manner and were capable of allostimulatory function. However, the stimulatory capacity of these cornea-derived dendritic cells (DCs) was suppressed compared with splenic controls. These results demonstrate for the first time that the cornea is endowed with resident DCs that are universally MHC class II− but that are capable of expressing class II antigen after surgery and migrating to draining LNs of allografted hosts. These data refute the tenet that the cornea is immune privileged due to lack of resident lymphoreticular cells or due to antigenic sequestration from systemic immunity.