Langerhans cells, orthotopic corneal allografts, and direct and indirect pathways of T-cell allorecognition

PURPOSE. TO determine after orthotopic corneal allografting the role of Lan gerhans cells in activation of T cells via the direct and indirect pathways of allorecognition and the relationship between these pathways and the rap idity of graft rejection. METHODS. Corneas from eyes of normal mice and from eyes after superficial c auterization were grafted to eyes of major histocompatibility complex (MHC) and/or minor histocompatibility (H)-disparate recipient mice; The grafts w ere analyzed through time for content of class II MHC-bearing Langerhans ce lls and for rejection or acceptance. Graft recipients were evaluated for ac quisition of delayed hypersensitivity (DH) and cytotoxic T cells (Tc) direc ted at donor MNC and minor H alloantigens. RESULTS. Langerhans cells migrated more rapidly into epithelium of cauteriz ed grafts than normal grafts. Unlike normal grafts, the vast majority of ca uterized allografts were rejected within 2 weeks. Normal grafts induced nei ther DH nor Tc directed at donor MHC antigens, whereas cauterized grafts in duced both DH and Tc specific for donor MHC. All grafts induced DH directed at donor minor H antigens, but only rejected grafts correlated with acquis ition of Te directed at donor minor H antigens. CONCLUSIONS. The rapidity of orthotopic corneal allograft rejection correla ted with density of Langerhans cells within epithelium and with acquisition of donor-specific DH and Tc. Although recipient-derived Langerhans cells p romoted minor H-specific, self-MHC-restricted T cells (indirect pathway) an d subacute graft rejection, donor-derived Langerhans cells promoted early, acute rejection in conjunction with allogeneic MHC-specific Tc (direct path way).