The critical role of lymph nodes in corneal alloimmunization and graft rejection

PURPOSE. To elucidate the role of draining cervical lymph nodes (CLNs) in c orneal alloimmunity. METHODS. Fully mismatched orthotopic corneal transplan tation was performed in BALB/c hosts that had their CLNs excised before tra nsplantation (CLN-). Normal hosts (CLN+), splenectomized mice (Sp(-)), and those without either CLNs or spleen (CLN-/Sp(-)) served as comparison group s. To determine the contribution of CLNs to alloimmunity more directly, CLN - mice were reconstituted by grafting LNs from other BALB/c mice to their c ervical lymphatic chains, thus deriving CLN-/+ mice. Tetramethyl rhodamine isothiocyanate's (TRITC) flow to draining CLNs was used as a measure of aff erent lymph flow. Graft survival and allospecific delayed-type hypersensiti vity (DTH) were used as measures of alloreactivity. RESULTS. Fifty percent of normal control and 12% of Sp(-) hosts accepted th e allografts. In contrast, 100% of CLN- and 88% of CLN-/Sp(-) hosts accepte d allografts indefinitely (R < 0.01). Additionally, all CLN- hosts failed t o demonstrate allospecific DTH (P < 0.001). CLN-/+ mice reconstituted with LN from naive animals showed graft survival rates and DTH responses that we re indistinguishable from those of naive CLN+ mice. Of particular interest, however, is that mice reconstituted with CLNs from hosts with rejected cor neal grafts had swift rejection of subsequent corneal grafts and exhibited strong donor-specific DTH. In contrast, mice reconstituted with CLNs from h osts with accepted corneal grafts showed rejection of subsequent corneal gr afts in a manner that was indistinguishable from rejection in naive CLN+ ho sts. CONCLUSIONS. Draining CLNs play a critical role in allosensitization and re jection. In contrast to the spleen, draining CLNs do not appear to play a c ritical role in tolerance induction in corneal transplantation.