Yamagami, SatoruDana, Reza2017-11-272001Satoru Yamagami and M. Reza Dana. 2001. "The Critical Role of Lymph Nodes in Corneal Alloimmunization and Graft Rejection." Investigative Ophthalmology & Visual Science 42, no.6:1293-12980146-0404http://nrs.harvard.edu/urn-3:HUL.InstRepos:34388136purpose. To elucidate the role of draining cervical lymph nodes (CLNs) in corneal alloimmunity. methods. Fully mismatched orthotopic corneal transplantation was performed in BALB/c hosts that had their CLNs excised before transplantation (CLN−). Normal hosts (CLN+), splenectomized mice (Sp−), and those without either CLNs or spleen (CLN−/Sp−) served as comparison groups. To determine the contribution of CLNs to alloimmunity more directly, CLN− mice were reconstituted by grafting LNs from other BALB/c mice to their cervical lymphatic chains, thus deriving CLN−/+ mice. Tetramethyl rhodamine isothiocyanate’s (TRITC) flow to draining CLNs was used as a measure of afferent lymph flow. Graft survival and allospecific delayed-type hypersensitivity (DTH) were used as measures of alloreactivity. results. Fifty percent of normal control and 12% of Sp− hosts accepted the allografts. In contrast, 100% of CLN− and 88% of CLN−/Sp− hosts accepted allografts indefinitely (P < 0.01). Additionally, all CLN− hosts failed to demonstrate allospecific DTH (P < 0.001). CLN−/+ mice reconstituted with LN from naïve animals showed graft survival rates and DTH responses that were indistinguishable from those of naïve CLN+ mice. Of particular interest, however, is that mice reconstituted with CLNs from hosts with rejected corneal grafts had swift rejection of subsequent corneal grafts and exhibited strong donor-specific DTH. In contrast, mice reconstituted with CLNs from hosts with accepted corneal grafts showed rejection of subsequent corneal grafts in a manner that was indistinguishable from rejection in naïve CLN+ hosts. conclusions. Draining CLNs play a critical role in allosensitization and rejection. In contrast to the spleen, draining CLNs do not appear to play a critical role in tolerance induction in corneal transplantation.en-USJournal Article2017-06-1820012017-11-27